Prevalence of hypertension obesity diabetes and metabolic syndrome in nepal,jan fabre choreography,epidemiology of childhood type 2 diabetes in the developing world - Good Point

Please, complete the form with your suscription data.If you are a member of the Spanish Society of Cardiology, you can use the same login and password that you use to access the Society's website. Even though various studies have suggested that subepicardial fat may play a role in the development of coronary heart disease, the exact mechanism requires further study. For several years it was believed that obesity could cause heart failure only via intermediary mechanisms such as hypertension or coronary heart disease, but recent studies have demonstrated that other factors could be implicated in the origin of obesity-associated cardiomyopathy. The prevalence of atrial fibrillation and obesity has significantly increased in recent years. Other physiopathological mechanisms could also be implicated in the association between obesity and sudden death or ventricular arrhythmias. There is a direct and J-shaped relationship between BMI and the incidence of coronary heart disease.
Several studies have compared the use of the BMI to determine body fat with techniques known to accurately measure body composition.
The waist-to-hip ratio has been used as a proxy measure of body fat distribution to assess health issues associated with obesity. Although the word obesity is defined as excessive fat, in clinical practice obesity is not diagnosed by measuring fat or body composition. The main aim of obesity therapy is weight loss and maintenance by dietary interventions and increased physical activity.
Apart from weight loss, these drugs also reduce abdominal circumference and systolic and diastolic blood pressure. Although several studies have demonstrated abnormalities in cardiac structure and function in obese patients, few studies have assessed the effect of bariatric surgery on cardiac morphology. Science, Technology and Medicine open access publisher.Publish, read and share novel research. Mental Function and ObesityNobuko Yamada-Goto1, Goro Katsuura1 and Kazuwa Nakao1[1] Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan1. Cardiovascular and Renal Complications in Obesity and Obesity-Related Medical Conditions: Role of Sympathetic Nervous Activity and Insulin ResistanceKazuko Masuo1, 2 and Gavin W. Alberi KG, Zimmet PZ,1998Definition, diagnosis and classification of diabetes mellitus and its complications. Anderson EA, Hoffman RP, Balon TW, Sinkey CA, Mark AL.1991Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans.
Prevalence Of Hypertension Obesity Diabetes And article Healthy people 2010 identified overweight and obesity as 1 of 10 leading health indicators and called for a reduction in the proportion of children and adolescents. Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health.
Above you can read article and ebook that discuss about Prevalence Of Hypertension Obesity Diabetes And . Copyright © 2014 Special Gift, All trademarks are the property of the respective trademark owners.
There has been a steady increase in the worldwide prevalence of preschooler overweight and obesity and has reached 7% or 43 million in 2010. Even in the context of rising obesity rates in childhood, there is a substantial change in the weight status between adolescence and young adulthood.
The presence of obesity in childhood and adolescence is associated with increased evidence of atherosclerosis at autopsy and of subclinical measures of atherosclerosis on vascular imaging. Children are now having health problems that were previously seen only in adults – like heart disease, diabetes and high blood pressure. Pediatric obesity can lead to metabolic syndrome, diabetes, hypertension, obstructive sleep apnea, dyslipidemia all of which can lead to premature CVD.See Figure 110. Overweight children run the risk of developing diabetes, a risk factor for CVD in young adulthood.14 Developing nations, especially India are seeing sharp rises in the number of children with diabetes (Type 2) due to changes in lifestyle. Substantial shifts in overweight and obesity occur between adolescence and young adulthood;  There is 50% increase  of overweight from 20% to 33% and a doubling of obesity 4% 7% . The investigators concluded that an elevated BMI in adolescence, including one that is well within the range currently considered to be normal, constitutes a significant risk factor for obesity-related disorders in midlife. Many factors have combined to fuel the obesity epidemic in children such as increased consumption of energy-dense food, decreasing physical activity and the increasingly easy accessibility of food.
Schools are becoming a less and less healthy environment where children are not protected from bad diets or encouraged into physically active lifestyles. Because of the link between food advertising and childhood obesity authorities in the UK have banned the advertising of high fat, salt and sugar products in or around programmes made for children or that are likely to appeal to children. Disclaimer : Please note that the content on CADI Research Foundation attempts to define practices that meet the needs of most patients in most circumstances. Home» Mediterranean Diet Newsletter » Could you be at risk for Metabolic Syndrome?
Many individuals have health issues, such as high cholesterol, increased blood pressure, high blood sugar levels, or are obese. Its prevalence has increased in almost every continent and has probably increased in all the developed countries.
A positive association has been observed between BMI and CRP in adults and children.27 The mechanisms by which obesity leads to elevated CRP have not been fully explained.
Outline of subepicardial fat by two-dimensional echocardiography in the parasternal long-axis view.
Longitudinal studies that have evaluated the incidence of cardiovascular disease and studies that have assessed the effects of continuous positive airway pressure therapy have suggested a causal association between OSA and several cardiovascular disorders.
This cutoff was selected because the mortality curve in several epidemiological studies increased at this value. The results of these studies have varied, but the majority demonstrated that the standard BMI cutoff values used to define obesity appear to underestimate body fat. Measures of central obesity are very useful in improving the assessment of obesity-associated risk. In fact, there is no consensus on the percentage of body fact considered to be normal. Prevalence of metabolic syndrome, risk factors and history of cardiovascular disease in normal-weight individuals by percentile body fat.
However, maintaining the weight loss using these interventions is difficult and relapse rates are high. Obesity is associated with several cardiovascular diseases and is not only linked to coronary heart disease, but also to abnormalities in heart rate and ventricular function. Impairment of fear-conditioning responses and changes of brain neurotrophic factors in diet-induced obese mice. Schematic diagram potential interactions between metabolic hunger and hedonic hunger which regulate food intake. Percentage of food addiction diagnosis according to the Yale Food Addiction Scale as a function of weight category. IntroductionObesity is defined as a high body mass index (BMI) with a large amount of adiposity.
Potential pathophysiological mechanisms in obesity, hypertension and type2diabetes (T2DM)4. Subjects with deteriorations of renal function (creatinine clearance) carried higher frequency of the Gly16 allele of Arg16Gly, the ?2-adrenoceptor polymorphisms6. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. This is expected to reach 9% or  60 million, by 2020.2 The prevalence of preschooler obesity is similar in Africa but lower in Asia.
Given  that the trend toward childhood obesity starts as early as age six months, the infant and preschool years are considered possible critical periods for such interventions and programs. The he extent of continuity depends on both the severity and persistence of adiposity in adolescence. Although the risk of diabetes is mainly associated with increased BMI close to the time of diagnosis, the risk of CHD is associated with an elevated BMI both in adolescence and in adulthood, supporting the hypothesis that the processes causing incident CHD, particularly atherosclerosis, are more gradual than those resulting in incident diabetes. A healthy lifestyle with regular physical activity is critical for prevention of elevated BMI in childhood.
Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Prevalence of overweight and obesity in Australian children and adolescents: reassessment of 1985 and 1995 data against new standard international definitions.
Childhood obesity in Asian Indians: a burgeoning cause of insulin resistance, diabetes and sub-clinical inflammation. Overweight and obesity between adolescence and young adulthood: a 10-year prospective cohort study. Predictive associations between alternative measures of childhood adiposity and adult cardio-metabolic health. Overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment.
However, everyone is unique, and the extent to which the information applies specifically to you should be a key point of discussion between you and your cardiologist or health care provider. An integrated proposal to explain the epidemic of cardiovascular disease in a developing country. The different physiopathological mechanisms by which obesity is associated with cardiovascular disease are complex and are not limited to factors such as diabetes mellitus type 2, hypertension or dyslipidemia. It is a multiple-action hormone, whose possible effects include increased sympathetic activity that promotes thrombosis and increases blood pressure and heart rate.
Other studies have shown that subepicardial fat supplies free fatty acids for energy production and cytokine synthesis. OSA causes acute and chronic stress that could predispose to myocardial ischemia during sleep. Since BMI cannot differentiate between muscle mass and fat, individuals who have coronary heart disease and are moderately overweight or obese may have more preserved muscle mass. All these methods correlate well with the total quantity of visceral fat in grams as measured by more accurate techniques such as computed tomography or magnetic resonance imaging. Abdominal circumference has shown reasonable reproducibility in research studies, but variability could be a significant issue in clinical practice. Sibutramine and rimonabant reduced triglyceride concentrations and increased HDLc concentrations.
This association is due to multiple mechanisms and not only to hypertension, diabetes mellitus or dyslipidemia.
Food intake is controlled by complex neural system that reflects the fundamental biological importance of adequate nutrient supply and balance.
The prevalence of cognitive impairment, schizophrenia, depression, and eating disorder increases in obesity.
A chronic excess energy intake above energy expenditure leads to abnormal or excessive fat accumulation.
IntroductionElevated sympathetic activation, as assessed using a variety of indices, has been observed in lean hypertensive and diabetic patients, and obese individuals [Huggett et al.
Few adolescents who peak into obesity or are persistently overweight achieve a normal weight in young adulthood. The ultimate judgment regarding your care must be made by you and your healthcare provider together, in light of circumstances specific to you as a patient. A diseased metabolism can result in type 2 diabetes, heart attacks, stroke, or sudden death. Endothelial dysfunction induces chemotaxis of adhesion molecules and the differentiation of monocytes into macrophages. On the other hand, studies on postoperative cardiac patients have not demonstrated any increase in the risk of atrial fibrillation in obese patients.
Hip circumference is measured at the level of the major trochanters or at the greatest circumference at the level of the buttocks. The diagnosis of obesity should include measurements of total body fat content and its distribution. Freezing percentages of CD and DIO mice in the contextual conditioning test were measured every minute for 5 min.
Metabolic hunger regulated by homeostatic metabolic status designed to preserve energy balance and protect minimal levels adiposity. Repeated use of addictive drugs produces multiple changes in the brain that may lead to addiction. The prevalence of metabolic dysregulation, such as insulin resistance, hypertension, and dyslipidemia, in other words, metabolic syndrome and obesity are often comorbid in mental disorder. Normally, humans and other mammals have an extraordinary ability to match food intake to energy expenditure over long periods so that body weight and adiposity are maintained at near-constant levels. Although there are many factors that increase your chances of having this disorder, such as age, race, history of diabetes, or obesity, there are ways to take charge of your health with your diet. Although the management of obesity is difficult, a comprehensive management program can lead to favorable outcomes. Freezing percentages of CD and DIO mice in the cued conditioning test were measured every minute for 3 min.
These findings speculate that there are mutual interaction between obesity and mental disorder, common vulnerability and treatment possibility towards obesity and mental disorder. The Mediterranean diet is high in monounsaturated fatty acids, fruits, vegetables, whole-grain cereals, and low-fat dairy products, coupled with fish, poultry, nuts, legumes, and a low consumption of red meat. These findings also support the idea that measures of central obesity are better markers of fat-related cardiovascular risk, particularly in patients with coronary heart disease. Reward circuit which is mainly regulated by the midbrain dopamine system from the VTA to NAc, is the main pathway of hedonic hunger. After findings on the hypothalamus as the center of energy regulation in 1940’s, the central nervous system came to the forefront of attention in the pathophysiology of obesity.
Similarly, many epidemiological studies have shown that hypertensive patients, even those without increased adiposity, display a higher prevalence of insulin resistance, thereby indicating the possible association between sympathetic activation and insulin resistance in the pathogenesis of hypertension [Esler et al. This specific way of eating, is associated with a lower prevalence and slower progression of metabolic syndrome. Cardiovascular and renal complications in obesity, obesity-related hypertension and diabetes5.1. Individuals who followed a Mediterranean diet similar to Ayhan’s Mediterranean Diet Plan were shown to improve individual components of metabolic syndrome (waist circumference, glucose levels, lipids and blood pressure) significantly. Circulating signals of energy availability, leptin, ghrelin, glucose, and insulin are thought to regulate food intake mainly via the hypothalamus, but recent studies show that they also regulate food intake via many extra-hypothalamic regions. Repeated taking of palatable food produces multiple changes in the brain that may lead to obesity. Clinical studies have revealed that obesity is comorbid with several forms of mental disorder [3-5].
Hyperglycemia and insulin resistance as risk factors of cardiovascular complications in type 2 diabetes5.2. Epidemiological studies show that obesity is strongly related to cognitive impairment, including Alzheimer’s disease and mood disorder [6, 7]. Sympathetic nervous activity as a risk factor for cardiovascular complications and renal complications5.3. Obesity is also positively correlated with several other forms of mental disorder in general population samples.
Overweight and obesity is a growing problem across the globe and has reached “epidemic” proportions.
These findings suggest that obesity can affect mental function and change neural plasticity.
The prevalence of diabetes, especially type 2 diabetes, and hypertension are significantly increased with the prevalence of obesity.
Obesity, itself, and type 2 diabetes and hypertension associated with obesity are known to be more closely linked with insulin resistance and elevated sympathetic nervous activity.
Moreover, there is the possibility that mental disorder acts as a trigger of the development of obesity. It has been well documented that obesity, hypertension, and diabetes are risk factors for subsequent cardiovascular and renal complications. Understanding the bidirectional interaction of obesity and mental disorder should help prevent and treat obesity.
Many patients are both diabetic and hypertensive while they are obese, but not all diabetic patients have hypertension, indicating that insulin resistance is not the only mechanism for blood pressure elevation in diabetic-hypertensive patients.
This review is aimed at highlighting the mental functions related to obesity, from basic research including our recent works to clinical findings.2. Several investigators have reported that sympathetic nervous activation plays an important role in cardiovascular complications in patients with hypertension, diabetes, and obesity.Sympathetic nervous activation accompanying insulin resistance is closely linked with left ventricular hypertrophy in otherwise healthy subjects [Masuo, et al. In addition, sympathetic activation may predict the development of renal injury in healthy normotensive subjects [Masuo, et al. Being overweight or obesity are defined as having abnormal or excessive fat accumulation that presents a risk to health.
The World Health Organization (WHO) defines obesity for adults based on overweight and obesity ranges determined by body mass index (BMI), a person’s weight (in kilograms) divided by the square of height (in meters).
Weight loss associated suppression of sympathetic nervous activity is associated with improvement of insulin sensitivity and resultant improvement in renal function in obese patients [Masuo, et al. Furthermore, weight loss improved the prevalence of left ventricular hypertrophy [Masuo, et al.
2008], which is one of the predictors for future cardiac complications, renal complications (injury) [Masuo, et al.
BMI provides the most useful population-level measure of being overweight and obesity as it is the same for both sexes and for all ages of adults. 2011].These findings suggest that elevated sympathetic nerve activity associated with insulin resistance may contribute to the onset and maintenance of cardiovascular and renal complications in diabetes, and hypertension in obesity.
However, WHO points out that it should be considered as a rough guide because it may not correspond to the same degree of fatness in different individuals.
Furthermore, genetic polymorphisms of the ?2- and ?3-adrenoceptor gene have been associated with obesity [Masuo, et al. It was reported that South Asian, East Asian, and African-American developed diabetes at a higher rate, at an earlier age, and at lower ranges of BMI than their white counterparts [10]. Body fat distribution, rather than overall adiposity, influences serum lipids and lipoproteins in healthy men independently of age. In 2000, The Asia-Pacific Perspective: Redefining Obesity and Its Treatment recommended different ranges for the Asia-Pacific regions based on risk factors and morbidities.
2005 & 2010} in epidemiological studies and may also be implicit in the close relationship between insulin resistance and sympathetic nerve activation. Definition of obesity in East AsiaSubstantial differences in national and local environments with genetic variances produce the wide variation in obesity prevalence in the world.
The prevalence of obesity in adults is lower in East Asia including Japan compared with the USA [12]. In East Asia, China, Japan, South Korea and Taiwan have their own criteria of overweight and obesity.
In Japan, according to the Japan Society for the Study of Obesity 2011 (JASSO), the BMI values considered as being underweight or in the normal range are the same as the WHO criteria [13]. These investigations suggest that ?2-adrenoceptor polymorphisms are related to sympathetic activation and insulin resistance and may contribute to cardiovascular- and renal complications in obesity and obesity-related hypertension or type 2 diabetes.This chapter will provide a synthesis of the current findings on the mechanisms of the onset and maintenance of cardiovascular and renal complications in obesity, hypertension and type 2 diabetes, with a particular focus on sympathetic nervous activity and insulin resistance.
A better understanding of the relationships between sympathetic nervous activity and insulin resistance in these important clinical conditions might help with the clinical treatment of diabetes and hypertension in obesity and prevent further cardiovascular and renal complications in this at risk group. Prevalence of type 2 diabetes and hypertension in obesityThe clustering of cardiovascular risk factors associated with obesity, in particular abdominal obesity, is well established [Athyrus, et al. Sex matters: secular and geographical trends in sex differences in coronary heart disease mortality.
The prevalence of obesity and overweight increased in the United States between 1978 and 1991 [Mokdad, et al. Mortality and complicationsThe BMI classification scheme for weight status is based on data obtained from large epidemiological studies that evaluate the relationship between BMI and mortality [17]. The National Health and Nutrition Examination Survey (NHANES) I (1971-1974), NHANES II (1976-1980), and NAHNES III (1988-1994) were conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention (CDC). Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P, et al; INTERHEART Study Investigators. Secular trends in mortality by stroke subtype in the 20th century: a retrospective analysis. These data from the continuous NHANES studies have showed that the prevalence of obesity and overweight people increased significantly in the United States between 1960 and 2003 [Preis, et al.
Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. On the other hand, the positive correlation between obesity and many health problems both independently and in association with other diseases are clearly observed. In adults, the health complications associated with obesity increase linearly with increasing BMI until the age of 75 years [18, 22]. Evidence from several studies indicates that obesity and weight gain are associated with an increased risk of hypertension [Masuo, et al. In particular, obesity is associated with the development of type 2 diabetes mellitus, coronary heart disease, an increased incidence of certain forms of cancer (colon, breast, esophageal, uterine, ovarian, kidney, and pancreatic), respiratory complications (obstructive sleep apnea), and osteoarthritis of large and small joints [23]. Clinical aspects related to psychiatry in obesityFrom the viewpoint of the endocrinologist, obesity is often comorbid with eating disorders, especially binge-eating disorder, which is thought to be present in 20-40% of obese patients [25]. 1997], and that intentional weight loss reduces the risk that overweight individuals will develop hypertension [Masuo, et al. Many lines of evidence suggest that obesity and depression often comorbid and might be functionally related to each other [3, 26-30].
High rates of obesity among individuals with binge eating disorder, bipolar disorder, major depressive disorder, anxiety disorders, schizophrenia, personality disorders, and other diagnoses were also observed [3, 5, 27, 31]. The link between such mental disorder and obesity is likely to be bidirectional: obesity can lead to mental disorder and, in turn, mental disorder can be an obstacle to treatments of obesity and attaining long-term weight-loss goals, thereby contributing to weight gain [25]. Evidence also indicates that obesity negatively impacts on prognosis of many kind of illness. Recent large cohort studies have showed an increasing prevalence of obesity in children and, importantly, obesity in children is strongly associated with several major health risk factors, including type 2 diabetes mellitus and hypertension [Hedley, et al.
2004].Focusing on the close associations between obesity, hypertension and diabetes, the NHANES and the Behavioural Risk Factor Surveillance System (BRFSS) investigations [Mokdad, et al. Associations between obesity and psychiatric illness are also documented in men but in more moderately overweight individuals [5].
2003] showed very close relationships between the prevalence of obesity, hypertension, and diabetes. Obese individuals are subject to weight-based stigmatization in a variety of settings, and generally report poorer quality of life compared with lean individuals [4, 5].From the viewpoint of the psychiatrist, obesity is defined as eating disorder. 2009] showed that diabetic subjects had a 2-fold higher mortality risk consisting of cardiovascular and non-cardiovascular mortality. Anorexia nervosa, bulimia nervosa, eating disorders not otherwise specified, and obesity are categorized as eating disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV TR [32]. Sympathetic nervous activity in obesity, hypertension and diabetesThe sympathetic nervous system represents a major pathophysiological hallmark of both hypertension and renal failure, and is an important target of the therapeutic intervention [Grassi, et al.
Even with the gender specificity, eating disorders are thought to share dysregulation of common neuronal pathways with obesity [33]. Some population of obesity is characterized as mental disorder with “compulsive food consumption” similar to drug addiction and suggested to be included as a mental disorder in the DSM-V [5].
The pathophysiology of anorexia nervosa draws attention as it is thought to be the opposite phenotype of obesity [Figure 1]. The sympathetic nervous system participates in regulating the energy balance through thermogenesis.
Functional magnetic resonance image (fMRI) study showed that brain reward circuits are more responsive to unexpected food stimuli and more sensitive in dopamine-related pathways in anorexia nervosa, but are less responsive and less sensitive in obese women [33]. Reduced energy expenditure and resting metabolic rate are predictive of weight gain (obesity). Cardiovascular diseases in the developing countries: dimensions, determinants, dynamics and directions for public health action. Moreover, a recent fMRI study suggested that self starvation in anorexia nervosa may be driven by inappropriately assigned desire and pleasure associated with food restriction, somehow related to dependence [34]. It is also widely recognized that insulin resistance or hyperinsulinemia relates to obesity [Minicardi, et al.
They might perpetuate and reinforce the desire to not eat to change persistent stress, such as low self-esteem and social rejection into a positively experienced state [35]. Bulimia nervosa is another severe eating disorder characterized by the presence of episodic binge eating followed by extreme behaviors to avoid weight gain, such as self-induced vomiting, use of laxative or excessive exercise [32]. Individuals with bulimia nervosa present with fear of gaining weight, as well as food and body weight-related preoccupations, are at normal or often high-normal weight. Many epidemiological and clinical studies have shown a close relationship between sympathetic nervous system activity and insulin levels in obesity [Masuo. These abnormal eating behaviors observed in anorexia nervosa and bulimia nervosa are also difficult to treat and contain life-long risk of relapse [36].


Figure 1.Postulated shared mechanisms related to reward circuits of anorexia nervosa and obesity.
The sense of hunger regulated by reward circuits might be the key component of obesity and anorexia nervosa.How about the personality of obesity? Several studies of longitudinal design have examined the effect of body weight changes (weight loss or weight gain) on sympathetic nervous system activity and insulin sensitivity (fasting plasma insulin levels and the (homeostasis model assessment of insulin resistance, HOMA-IR).
Elevations of sympathetic nervous system activity and insulin levels during weight gain [Masuo, et al.
Body weight reflects our behaviors and lifestyle and contributes to the way we perceive ourselves and others. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
Personality traits are defined by cognitive, emotional, and behavioral patterns that are likely to contribute to unhealthy weight and difficulties with weight management. It is quite difficult to clarify personal traits, but there are many clinical studies on the personality of obesity using certain questionnaires [37-41]. 2003], and reductions of sympathetic activity and insulin levels during weight loss [Anderson, et al. Overweight individuals are prone to depressive state, have a poor body image, are evaluated negatively by others, and are ascribed traits based on their body size [42-45]. From the Baltimore Longitudinal Study of Aging (BLSA), which is a longitudinal study of more than 50 years on a large number of people (n = 1,988), high neuroticism and low conscientiousness, which are related to difficulty with impulse control, were associated with weight fluctuations [40]. Low agreeableness and impulsivity-related traits predicted a greater increase in BMI across the adult life span in the same study [40].
While these longitudinal studies have clearly shown that heightened sympathetic nerve activity and insulin resistance are closely linked to obesity (weight gain), the onset of obesity and the maintenance of obesity, it remains to be elucidated, whether sympathetic hyperactivity or insulin resistance is the prime mover. Personality traits are reported to be a useful tool for predicting diet-induced weight loss and management, which may offer ways to achieve appropriate weight loss and management strategies for individuals [46-47].To date, however, there is no evidence to support a direct interaction between obesity and these personality traits. The response of the sympathetic nervous system to change in plasma insulin levels after oral glucose loading (oral glucose tolerance test) are different between subjects with and without insulin resistance [Masuo, et al. It is not clear that how these mental disorders and personality traits are related to the natural course of obesity.
Brain inflammation and obesityAdiposity causes chronic low-grade systemic inflammation, which in conjunction with a high calorie diet may contribute to diseases associated with obesity [48-49]. Sanchez-Castillo CP, Velasquez-Monroy O, Lara-Esqueda A, Berber A, Sepulveda J, Tapia-Conyer R, et al. A growing body of evidence implicates immune cell-mediated tissue inflammation as an important mechanism linking obesity to insulin resistance in metabolically active organs, such as the liver, skeletal muscle, and adipose tissue [48-49].
Recently, changes in the sympathetic nerve firing pattern were observed with sympatho-inhibition during weight loss [Lambert, et al. Diabetes and hypertension increases in a society with abdominal obesity: results of the Mexican Nacional Health Survey 2000. Peripheral inflammation passes through or bypasses the blood-brain barrier [50-51], and stimulation of neural afferents at the site of local peripheral inflammation induces an inflammatory reaction within the central nervous system [52-53]. The saturated free fatty acids, palmitic acids and lauric acid, have been shown to trigger inflammation in cultured macrophages [54]. Saturated long-chain fatty acids were demonstrated to activate inflammatory signaling in astrocytes [55].
Microglia, macrophage-like cells of the central nervous system that are activated by pro-inflammatory signals causing local production of specific interleukins and cytokines, play a pivotal role in brain inflammation [48-49, 53, 55-57]. Experimental studies in animals have confirmed neurologic vulnerability to obesity and a high-fat diet and further demonstrated that diet-induced metabolic dysfunction leads to increased brain inflammation, reactive gliosis, and vulnerability to injury, especially in the hypothalamus [49, 56, 58-59].
These observations provide the evidence of a strong linkage between the activity of the sympathetic nervous system and insulin levels. Hypothalamic inflammation contributes to obesity pathogenesis through the development of central leptin resistance [49, 56]. Leptin resistance is a physiological condition in which high concentrations of leptin neither reduce food intake nor increase energy expenditure, as observed in obese humans and a rodent model of diet-induced obesity (DIO) [60]. 2003] examined muscle sympathetic nerve activity (MSNA) in four groups of subjects, patients with essential hypertension and type 2 diabetes, patients with type 2 diabetes alone, patients with essential hypertension alone, and healthy normotensive controls.
Immune-related molecules, including proinflammatory cytokines, IL-1?, TNF-?, and IL-6, altered expression levels of many genes in the hypothalamus [49, 56, 58]. They found higher MSNA in the hypertensive-type 2 diabetic patients as compared with hypertensive alone patients or type 2 diabetic alone patients, and higher MSNA in hypertensive alone patients or type 2 diabetic alone patients as compared with healthy normotensive controls. Fasting insulin levels were greater in hypertensive-type 2 diabetic patients and type 2 diabetic patients compared to hypertensive patients or healthy normotensive subjects. High-fat feeding increases suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase-1B (PTP1B) in the rodent hypothalamus [56, 58, 62].
These findings, although obtained in patients still under medication, provided evidence that type 2 diabetic patients had elevated sympathetic nerve activity regardless of the prevailing blood pressure levels, and that the combination of hypertension and type 2 diabetes resulted in an augmentation in sympathetic nerve activity and levels of plasma insulin.
Up-regulation of SOCS3, a member of a protein family originally characterized as negative feedback regulators of inflammation, inhibits insulin and leptin signaling by direct binding to their cognate receptors and targeting insulin receptor substrate (IRS) proteins for proteasomal degaradation [58]. Several investigations on the contributions of ?2- and ?3-adrenoceptor polymorphisms to type 2 diabetes also support a strong relationship between sympathetic nerve hyperactivity and insulin resistance in type 2 diabetes [Masuo, et al. The PTP1B is a signal termination molecule that inhibits both leptin and insulin signaling, also thought to be involved in leptin resistance [58, 62]. Diet-induced PTP1B overexpression in multiple tissues including the hypothalamus in obesity is regulated by inflammation [62]. Recent studies with animals and humans have shown that other brain structures, such as the hippocampus and orbitofrontal cortex, are also affected [53, 57, 63-64]. Many investigations have shown that insulin resistance, sympathetic nervous activation, and adrenoceptor polymorphisms play important roles in the onset and maintenance of obesity, type 2 diabetes and hypertension. These inflammatory changes induced by obesity and high-fat diet might be reversible from the results of animal studies. Resveratrol, an adenosine monophosphate-activated protein kinase (AMPK) activator and potent anti-inflammatory agent, attenuated peripheral and central inflammation in the hippocampus and improved memory deficit in mice fed a high-fat diet [57].
Insulin resistance in obesity, hypertension and type 2 diabetesInsulin resistance [Ferrannini, et al.
In another study, moderate and regular treadmill running exercise markedly decreased hypothalamic inflammation in high-fat diet fed mice [59].
Evidence of brain inflammation in human obesity has been accumulating based on biologic data and imaging studies by using MRI [46, 56].4. The clinical evaluation of insulin resistance is growing interest because it is a strong predictor and plays an important role in the development of the metabolic syndrome, type 2 diabetes mellitus and hypertension.
Table 1 shows the criteria for metabolic syndrome characterisation, as can be seen insulin resistance is prominent [Alberti, et al. Depression and other mood disordersObesity is associated with an increased risk of developing depression and a higher likelihood of current depression [3, 27-30].
Globalization, coca-colonization and the chronic disease epidemic: can the doomsday scenario be averted? Most obese individuals tend to have higher scores in depression, the projected increase in the rates of being overweight and obesity in future years could generate a parallel increase in obesity-related depression. According to the DSM-IV, an episode of major depressive disorder can be classified clinically as depression with melancholic features and depression with atypical features.
Unlike melancholic depression, which is characterized by a loss of appetite or weight, atypical depression and seasonal depression are characterized by decreased activity and increased appetite and weight. Table 2 summarizes the methods usually used in clinical and epidemiological studies (Table 2).
Obesity among these groups is sometimes a result of the ingestion of “palatable food”, which contains high amounts of fat and sugar [65]. The hyperinsulinemic-euglycemic glucose clamp method is the gold standard and may be suitable for research investigations in specialized laboratories, but the homeostasis model assessment of insulin resistance (HOMA-IR) or fasting plasma insulin concentrations is more practical for epidemiological studies comprising a large number of subjects. Also, major depression in female adolescence is linked with an increased risk of obesity in adulthood [66]. Hyperinsulinemia as a marker of insulin resistanceInsulin is an exceptional hormone in that its action is regulated not only by changes in concentration but also by changes in the sensitivity of target tissues. Among them, the involvement of leptin has been the subject of much attention as it has been implicated in depression associated with obesity [1]. Inadequate insulin action can be the consequence of: (i) insufficient insulin concentration at the site of action, (ii) decreased tissue (effectors) responses to insulin, or (iii) a combination of low concentration and a decreased response.
Leptin is reported to induce an antidepressant-like activity in the hippocampus, which is considered to be an important region for regulation of the depressive state, but not in the hypothalamus of rats [68]. Regulation of circulating insulin levels is mainly (but not exclusively) achieved by changes in secretory rates. Decreased plasma or CSF leptin levels were observed in major depressive disorder patient group compared with controls independent of BMI [69-70]. Nevertheless, the major determinant of insulin secretion, and therefore of plasma insulin concentration, is glucose.
These findings suggested that impairment of leptin action might contribute the physiology of depression. Any change in glucose concentration from the narrow normal range results in an insulin response appropriate to restore homeostasis. In obese rodents and humans, a high concentration of plasma leptin is observed with a blunted effect of leptin in suppressing food intake and increasing energy expenditure, which is termed “leptin resistance” [61].
Thus, changes in insulin sensitivity occur in various physiological states and pathological conditions.For any amount of insulin secreted by the pancreas, the biological response of a given effector is dependent on its insulin sensitivity. Based on these observations, we postulated that the development of depression associated with obesity might be due in part to impaired leptin activity in the hippocampus.Here we review our recent study on the central leptin action in depression associated with obesity [1]. The forced swimming test (FST) is widely accepted as a task that induces depressive behavior in depression research and has good reliability and high predictive validity for assessment of the depressive state and the detection of potential antidepressant-like activity in experimental animals.
Any decrease in insulin sensitivity (insulin resistance) is immediately translated into minute increases in blood glucose concentrations that will in turn act on the ?-cell to produce a compensatory stimulus of insulin secretion, leading to a degree of hyperinsulinemia that is approximately proportional to the degree of effector resistance. In this test, animals display “despair” behavior as observed as immobility and escape-oriented behaviors, in particular, by swimming [71-72]. Normal mice fed a control diet (CD) displayed such immobility and stress-induced despair in the FST. In steady-state conditions, this compensatory hyperinsulinemia prevents a more exaggerated hyperglycaemia. Subcutaneous administration of leptin significantly decreased the immobility time compared with saline treatment [Figure 2(A); 1]. The inability of ?-cells to enhance insulin secretion means that blood glucose will keep increasing until the level of hyperglycaemia produces an adequate ?-cell stimulus to attain the required insulin response.
Icv injection of leptin significantly decreased the immobility time of CD mice in the FST [Figure 2(B); 1].
When the ?-cell is unable to compensate for the prevalent insulin resistant state by further augmenting insulin secretion, hyperglycaemia continues to increase, producing impaired fasting glucose, impaired glucose tolerance and diabetes mellitus development.
DIO mice fed a 60% high-fat diet (HFD) for 16 weeks exhibited more depressive behavior compared with CD mice without exaggerated response of plasma corticosterone levels [Figure 2(C); 1]. Subcutaneous administration of leptin did not decrease the prolonged immobility time in DIO mice [Figure 2(D); 1].
Relationships between sympathetic nervous activity and insulin resistance in obesity, hypertension, and type 2 diabetesIt is widely recognized that insulin resistance or hyperinsulinemia relates to obesity [Ferrannini, et al. Moreover, in response to leptin, DIO mice did not exhibit an increase in the number of c-Fos-immunoreactive cells in the hippocampus, whereas leptin administration in CD mice has a significantly increased number of c-Fos immunoreactive cells in the hippocampus [1]. To examine whether the increased immobility time of DIO mice in the FST can be restored by diet substitution from HFD to CD, the diet of the DIO mice was changed from HFD to CD for the next 3 weeks. Many epidemiological and clinical studies have shown a close relationship between sympathetic nervous system activity and insulin levels in obesity [Anderson, et al. This led to significant reductions in body weight and fat weight and to the normalization of plasma levels of glucose, insulin, and leptin [1]. The immobility time in the FST in mice now given CD was significantly decreased and identical to that of the CD mice [1]. Moreover, subcutaneous administration of leptin significantly decreased the immobility time of FST in mice switched to CD [1].
These results are compatible with a previous report that diet substitution from HFD to CD in DIO mice restores leptin sensitivity as an anorexigenic action [73].
Several studies of longitudinal design have examined the effect of body weight changes (weight loss or weight gain) on sympathetic nervous system activity and insulin sensitivity (fasting plasma insulin levels and HOMA-IR). Brain-derived neurotrophic factor (BDNF) in the hippocampus is considered to play an important role in control of the depressive state. Injection of BDNF into the hippocampus in experimental animals has antidepressant effects in the FST, and this antidepressant effect induced by BDNF is inhibited by K252a, an inhibitor of the BDNF receptor tyrosine kinase B (TrkB) [74].
2007} and reductions of sympathetic nerve activity and insulin levels during weight loss [Masuo, et al. In our study, the hippocampal BDNF concentrations in DIO mice were significantly decreased compared with those of CD mice [Figure 2(E); 1]. Subcutaneous administration of leptin significantly increased BDNF concentrations in the hippocampus of CD mice but not in DIO mice [Figure 2(E); 1].
In summary, as shown in Figure 2F, in the lean state, leptin helps maintain normal body weight by acting on the arcuate nucleus of the hypothalamus (ARC), and provides an antidepressant-like action via hippocampal BDNF, whereas in the obese state, impaired leptin action even with a high concentration in plasma, may lead to rodent and human obesity occurring together with depression [Figure 2(F); 1].
These longitudinal studies have shown that heightened sympathetic nerve activity and insulin resistance are closely linked to obesity (weight gain), the onset of obesity and the maintenance of obesity. In addition, a calorie restricted diet and exercise may have different mechanism on weight loss-induced blood pressure reduction. Figure 2 shows changes in neurohormonal parameters over a 24-week period weight loss regimens with a mild calorie restricted diet alone, mild exercise alone, or a combination with a mild calorie restricted diet and mild exercise. Changes in patterns of growth and nutritional anthropometry in two rural modernizing Papua New Guinea communities. In addition, calorie restricted diet and exercise may have different mechanisms on weight loss-induced blood pressure reduction [Masuo, et al. Reduced energy expenditure and resting metabolic rate are predictive of weight gain and obesity development. The sympathetic nervous system participates in regulating energy balance through thermogenesis (Figure 1). Landsberg and other investigators hypothesized that energy intake stimulates hyperinsulinemia and sympathetic nerve activity resulting in blood pressure elevations in a cycle in order to inhibit thermogenesis.
Insulin-mediated sympathetic nerve stimulation in obese subjects is therefore considered part of a compensatory mechanism aimed at restoring the energy balance by increasing the metabolic rate [Landsberg. Clinical investigations show the relationship between insulin resistance and depression, but the underlying mechanisms are still unclear [76-77].
Hyperinsulinemia and insulin resistance in obese subjects are all part of a response to limit further weight gain via stimulating sympathetic nerve activity and thermogenesis [Landsberg, 2001]. Ghrelin is also play a potential role in defense against the consequences of stress, including stress-induced depression and anxiety and prevent their manifestation in experimental animals [82]. On the other hand, Julius and Masuo generated a hypothesis based on data from their longitudinal studies that increased sympathetic nerve activity in skeletal muscle causes neurogenic vasoconstriction, thereby reducing blood flow to muscle and consequently inducing a state of insulin resistance by lowering glucose delivery and uptake in hypertension and obesity.
These findings suggest that both leptin and ghrelin involve in mood regulation and might have antidepressant-like effect. Both blood pressure elevations and weight gain may reflect a primary increase in sympathetic nervous tone.
The target differences being treated by leptin or ghrelin in human depression are not known, yet.What kind of treatment is effective on depression associated with obesity? Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. One clinical study demonstrated the efficacy of a treatment combining behavioral weight management and cognitive behavioral therapy for obese adults with depression [81]. According to systematic review and meta-analysis on intentional weight loss and changes in symptoms of depression, obese individuals in weight loss trials experienced reduction in depression symptoms [80].
1997, 2000, and 2003] demonstrated that high plasma norepinephrine could predict future blood pressure elevations accompanying deterioration in insulin resistance. This was observed in HOMA-IR (homeostasis model assessments of insulin resistance) in nonobese, normotensive subjects using longitudinal studies. Cognitive impairment and Alzheimer’s diseaseEpidemiologic studies have demonstrated that the incidence of cognitive impairment is higher in obese individuals than in individuals with normal body weight [6, 24]. Toumilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, et al; Finnish Diabetes Prevention Study Group. From the study of Anstey et al., risks of cognitive impairment appeared to be highest for those with underweight and obese BMI in midlife [81].
Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. Increasing evidence suggests that obesity is associated with impairment of certain cognitive functions, such as executive function, attention, visuomotor skills, and memory [6, 82]. 1990] reported that clonidine prevented insulin resistance development in obese dogs over a 6-week period, suggesting that sympathetic nervous activity might play a major role in the development of insulin resistance accompanying blood pressure elevation. A higher prevalence of attention deficit hyperactivity disorder, Alzheimer’s disease and other cognitive impairment, cortical atrophy, and white matter disease is observed in obese individuals [83-84]. Postulated mechanisms include the effects of hyperglycemia, hyperinsulinemia, poor sleep with obstructive sleep apnea, and vascular damage to the central nervous system [7, 85]. 2000, 2001b, 2003, 2005a, 2012] might provide strong evidence for a close linkage of high sympathetic nervous activity accompanying insulin resistance with the onset of hypertension. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss.
C reactive protein, as well as inflammatory markers, is increased in subjects with greater adiposity and is associated with later-life cognitive impairment [86]. Heightened sympathetic nerve activity might play a major role in blood pressure elevations, and insulin resistance might play an ancillary mechanism for blood pressure elevation and genesis of hypertension. An Update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease From the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism.
White matter lesions and cerebral atrophy are more common in adults with a high BMI, and midlife measures of central obesity predict poor performance on tests measuring executive function and visuomotor skills [83-84, 87.
In hypertensive patients who already have heightened sympathetic nerve activity and insulin resistance, both heightened sympathetic nerve activity and insulin resistance are related to further blood pressure elevations. In animal studies, chronic dietary fat intake, especially saturated fatty acid intake, contributes to deficits in hippocampus- and amygdala-dependent learning and memory in rodents with diet-induced obesity by changes in neuronal plasticity [2, 88]. During weight loss with a mild calorie restricted diet, normalization of sympathetic activation measured by plasma norepinephrine was observed following significant weight loss and normalization of insulin resistance (HOMA-IR). Neural plasticity, long-term structural alterations of synapses, are regulated by several synaptic molecules including neurotrophic factors, such as BDNF, and have been demonstrated to be essential for hippocampal functions [89]. On the other hand, in exercise alone group, normalization of insulin resistance was observed, and then weight loss and suppression of sympathetic activation. In our recent study, cognitive behaviors in DIO mice in fear-conditioning test including both contextual and cued elements that preferentially depend on the hippocampus and amygdala, respectively, was significantly impaired [Figure 3(A); 2]. Fear-conditioning test is the method which assesses memory and learing by freezing behavior induced by electric foot shock. BDNF content in the cerebral cortex and hippocampus of DIO mice was significantly lower than that in CD mice [Figure 3(B); 2].
2012]Figure 2.When significant changes were observed comparisons between a calorie restricted diet vs.
Its receptor, full-length TrkB in the amygdala of DIO mice was significantly decreased compared to that in CD mice, although not in the cerebral cortex, hippocampus and hypothalamus [Figure 3(C); 2]. By contrast, neurotrophin-3 (NT-3), which is reported to act in the opposite direction to BDNF on neurite outgrowth and neural activities, was present at significantly higher levels in the hippocampus, amygdala and hypothalamus of DIO mice than that in CD mice [90-91, Figure 3(B); 2]. Its receptor, full-length TrkC, was not significantly different between CD and DIO mice [Figure 3(C); 2]. Figure 3.Impairment of fear-conditioning responses and changes of brain neurotrophic factors in diet-induced obese mice. 2012} showed the differences in mechanisms of weight loss-induced blood pressure reductions with neurohormonal parameters changes over 24 weeks with loss regimens (Figure 2). BMI and blood pressure decreased after significant reductions in both plasma norepinephrine and HOMA-IR (Figure 2). However, at least their hypotheses showed a strong linkage between sympathetic activation, insulin resistance, obesity and hypertension. 2004] reported attenuation of hemodynamic and energy expenditure responses to isoproterenol infusion in hypertensive patients. Their findings that a generalized decrease of ?-adrenergic responsiveness in hypertension supports the hypothesis that heightened sympathetic nerve activity through down-regulation of ?-adrenoceptor-mediated thermogenesis, may facilitate the development of obesity in hypertension. Electrophysiological studies in genetically obese Zucker rats with leptin-receptor deficiency demonstrated that long-term potentiation (LTP) of the hippocampal CA1 region, which is closely related to learning and the formation of memory and is regulated by N-methyl-D-aspartate (NMDA) and 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) receptors, is markedly impaired compared to that of lean rats [93]. Their results suggested that sympathetic nerve activity-induced hypertension may subsequently lead to the development of obesity. Streptozotocin-treated insulin deficient rats are reported to exhibit impaired cognition in the water maze test, which is dependent on the hippocampus [94]. Therefore, it is likely that impairment of the actions of leptin or insulin might be attributable to cognitive deficits in obesity and diabetes mellitus [61, 95].
1999] investigated the effects of the acute induction of hyperglycemia on sympathetic nervous activity and vascular function in eight young normal control subjects.
Muscle sympathetic nerve activity (MSNA) and forearm vascular resistance were measured before and during systemic infusion of 20% dextrose with low dose insulin with 60 min of hyperglycemia.
Metabolic hungerFood intake and energy expenditure are controlled by complex, redundant, and distributed neural systems that reflect the fundamental biologic importance of an adequate nutrient supply and energy balance. Metabolic hunger is regulated by a homeostatic metabolic status designed to preserve energy balance and maintain minimal levels of adiposity. Moreover, both acute and chronic hyperglycemia and hyperinsulinemia may enhance adrenergic vasoconstriction and decrease vasodilation in animal models (pithed rats) [Takatori, et al.
The hypothalamus serves to integrate nutrition and information from orexigenic and anorexigenic peptides that are sensitive to circulating leptin and other hormones [96-97].
The role of the hypothalamus in regulating food intake and body weight was established in 1940 by the classic experiments of Hetherington and Ranson [98].
Insulin causes forearm vasoconstriction in obese, insulin resistant hypertensive humans [Gudbjornsdotti, et al. Their destruction experiments demonstrated that the ventromedial hypothalamus resulted in hyperphagia and obesity [98]. Anand and Brobeck, in 1951, demonstrated that lesions of the lateral hypothalamus caused loss of feeding, inanition, and even death by starvation [99]. Thus, the concept arose of the lateral hypothalamic are serving as a “feeding center” and the ventromedial nucleus as a “satiety center” [100]. After more than 60 years since the Hetherington and Ranson experiments, much more precise mechanisms and the network between peripheral signals and the brain have been elucidated [97, 101]. 1999] found that hyperglycemia induced vasodilation in the forearm, but this vasodilation was not modified by hyperinsulinemia. Input signals such as sight, smell and taste allow the brain to decide whether or not it should engage in ingestive behavior. Sympathetic nervous activity and leptin in obesity and the metabolic syndromeInteractions between the sympathetic nervous system and leptin are widely acknowledged with each being able to influence the other. Gut-to-brain communication is increasingly recognized as playing an important role not just in the determination of meal size but also in overall food intake [97]. Indeed, the leptin system mediates some of its action through the sympathetic nervous system [Haynes, et al. Once absorbed, macronutrients are partitioned into either storage or immediate metabolism in various tissues [97]. The information from peripheral tissue including the gastric tract is relayed to the brain, especially to the hypothalamus and the brainstem by hormones [leptin, insulin, amylin, peptide YY (PYY), ghrelin, glucagon-like peptide-1 (GLP-1), and cholecystokinin (CCK)] and nutrient signals [glucose, free fatty acid, and amino acid] [97, 101]. Leptin, insulin and amylin deliver long-term afferent signals, PYY, GLP-1, and CCK deliver short-term meal related afferent signals and work for satiation, and ghrelin stimulate feeding. Using waist circumference as a screening tool to identify Colombian subjects at cardiovascular risk.
Vagal afferent neurons, whose cell bodies lie in the nodose ganglia, relay information from enteroendocrine cells of the intestinal epithelium and the enteric nervous system directly to the nucleus of the solitary tract in the brainstem [102]. During periods of hunger, the hypothalamus regulates the activity of the autonomic nervous system to promote fat release from white adipose tissue and trigger glucogenesis in the liver.
These changes in peripheral nutrient levels lead to a decrease in the levels of thyroid hormones, insulin and leptin, and to an increase in the level of ghrelin and corticosteroids, which increase food-seeking behavior through their effect on the brain [101]. 1996] investigated the effect of acute sympathetic nerve activation caused by exposure to cold on the expression of the leptin gene in white adipose tissue of lean mice, but not in obese mice. Through these pathways, an almost stable body weight can be maintained even under unpredictable and unstable environments.The ARC in the hypothalamus is the gateway of above hormones and signals in the brain [97, 101, 103]. From the ARC, the first-order neuronal network was observed of anorexigenic neuropeptides, proopiomelanocortin (POMC) and cocaine-amphetamine rerated transcript (CART), orexigenic neuropeptide, NPY and Agouti-related protein (AgRP) to other nuclei in the hypothalamus, the paraventricular hypothalamus (PVN), lateral hypothalamus (LH), and ventromedial hypothalamus (VMH) [97, 103].
These nuclei have a second-order neuronal network of output projection to other sites of the brain which regulate endocrine responses, autonomic responses, cognitive processing response plan, procurement actions, reward memory, aversive memory, social screen, competing behaviors, oro-and locomotor control, and autonomic control of peripheral tissue [97, 103]. Among these nucleus in the hypothalamus, LH works as a relaying point, connecting the hypothalamus with mesolimbic dopamine system and higher brain functions.


Melanin-concentrating hormone in the LH projects to the Nucleus accumbense (NAc) and many other brain areas including the amygdala, hippocampus, and cerebral cortex, and orexin in the LH project to the ventral tegmental area (VTA) and many other brain areas including the amygdala, hippocampus, and cerebral cortex [104]. These studies, together with others, indicate that both insulin resistance and leptin may be regulated by the sympathetic nervous system.Masuo et al.
From recent studies, first order neurons, which receive peripheral information and regulate food intake, are suspected to be present in other regions of the hypothalamus and extra-hypothalamus [1, 97, 105, 106]. Many hormones and neuropeptides, which were previously thought to energy regulator, have turned to regulate other higher brain functions, too.In human obesity, genetic predisposition is expressed mainly on the central melanocortin system. 2008] showed during oral glucose loading that plasma insulin and plasma norepinephrine increased in both insulin-sensitive and insulin-resistant subjects, but plasma leptin levels decreased in insulin-sensitive nonobese subjects and increased in insulin- resistant nonobese subjects.
Downstream targets of the central melanocortin system are implicated in food intake, meal choice, satiety and energy expenditure [107].
POMC is a large precursor protein that is processed into a variety of smaller products, including alpha melanocyte stimulating hormone (?-MSH), is an endogenous ligand of melanocortin 3 receptor (MC3R) and melanocortin 4 receptor (MC4R) in the brain [108].
2005] also reported the blunted responses of whole-body norepinephrine spillover, insulin, and plasma leptin during oral glucose loading in obese subjects with insulin resistance as compared to insulin sensitive subjects. Mutations in the MC4R in humans, the most commonly known monogenic cause of human obesity, have been associated with obesity, hyperphagia, tall -stature and hyperinsulinemia [110-113].
In subjects with the metabolic syndrome, weight loss with a low caloric diet diminished the whole-body and regional sympathetic nerve activity, as indicated by determinants of the whole-body norepinephrine spillover to plasma and muscle sympathetic nerve activity.
Common variants near MC4R were reported to influence fat mass, weight and obesity risk at the population level from genome-wide association data from people of European descent [114].
Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians?
Mutations in MC3R have been associated with obesity, hyper leptinemia and relative hypephagia [115]. Sympathetic nervous activity and insulin resistance in the metabolic syndromeThe metabolic syndrome is a cluster of abnormalities with basic characteristics being insulin resistance and visceral obesity. Mutation of leptin, which target is thought to be mainly the melanocortin circuitry in the brain, leptin receptor, and prohormone convertase-I were also reported in humans with severe early-onset obesity and intense hyperphagia [118-121]. Importantly, obesity and the metabolic syndrome are associated with significant co-morbidities, such as type 2 diabetes, cardiovascular disease, stroke, and certain types of cancers. Hedonic hungerSeveral lines of evidence have indicated that energy regulations are also modulated by extra-hypothalamic brain areas originally related to regulation of emotion and cognition, such as the NAc, amygdala, hippocampus and cerebral cortex [124].
2003 % 2004] demonstrated in a series of studies using microneurography (muscle sympathetic nerve activity, MSNA) that type 2 diabetic patients had elevated sympathetic nerve activity regardless of the prevailing level of blood pressure, and that the combination of hypertension and type 2 diabetes resulted in an augmentation in sympathetic nerve activity and levels of plasma insulin. The regulation of food intake by the hypothalamus interacts with reward and motivational neurocircuity to modify eating behavior. They also compared MSNA and insulin levels in 23 non-diabetic offspring of type 2 diabetic patients and 23 normal control individuals [Huggett, et al.
Reward circuitry, which is mainly regulated by the midbrain dopamine system from the VTA to the NAc, is the main pathway of hedonic hunger. This system is the main pathway in drug addiction and part of the motivational system that regulates responses to natural reinforcers such as drink, sex, social interaction and food [125].
This dopamine neuron express ?opioid receptors and receive projection of ?-aminobutyric acid (GABA) and dynorphin from the NAc [125]. Sympathetic activation occurred in not only subjects with the metabolic syndrome, diabetic patients, but also in normotensive non-diabetic offspring of patients with type 2 diabetes with the degree of activation being in proportion to their plasma insulin levels. Dopamine signaling within mesolimbic neurons mediates the willingness to engage in rewarding behaviors or “wanting”, whereas the pleasure associated with a particular reward or “liking” is attributed to mesolimbic opioid action [126]. This series of studies indicates the presence of a mechanistic link between hyperinsulinemia and sympathetic activation, both of which could play a role in the subsequent development of cardiovascular risk factors.5. Cardiovascular and renal complications in obesity, obesity-related hypertension and diabetesIt has been documented that patients with obesity, hypertension and type 2 diabetes frequently have cardiovascular and renal complications. Obesity was closely associated with an increase in blood pressure, left ventricular mass, and with early signs of disturbed left ventricular diastolic function [Wikstrand, et al. The amygdala ascribes emotional attributes including fear, together with memory and learning circuitry, and generates conditioned responses [2]. Figure 4.Schematic diagram potential interactions between metabolic hunger and hedonic hunger which regulate food intake. It is well known that sudden cardiac death is the most common cause of death in dialysis patients and is usually preceded by sudden cardiac arrest due to ventricular tachycardia or ventricular fibrillation [Alpert, et al.
Left ventricular (LV) mass and loading conditions that may affect LV mass are important determinants of corrected QT intervals (QTc) in normotensive severely obese subjects [Mukergi, et al. The RICARHD study (Cardiovascular risk in patients with arterial hypertension and type 2 diabetes study), was a multicenter and cross-sectional study, conducted in Spain and included 2,339 patients who were 55 years or more with hypertension and type 2 diabetes of greater than 6 months duration.
The combined presence of both hypertension and type 2 diabetes were associated with an increased prevalence of established cardiovascular diseases. Similarly, the presence of both cardiac and renal damage was associated to the higher prevalence of cardiovascular diseases [Cea-Calvo, et al.
Excessive activity of hedonic hunger in obesity might lead to the ingestion of more food, independent of metabolic hunger. Several recent models have emphasized the role of the dysregulation of hedonic hunger in the development and maintenance of obesity.
The Lifestyle Interventions and Independence for Elders (LIFE) study in 8,029 patients with stage II-III hypertension with LVH on ECG showed high prevalence of co-existence of LVH and albuminuria [Wachtell, et al.
Such “compulsive food consumption” was recently explained by an analogy to drug addiction as previously described [Figure 5]. Drug addiction is defined as the loss of control over drug use, or the compulsive seeking and taking of drugs despite adverse consequences [125].
In patients with moderately severe hypertension, LVH on two consecutive ECGs is associated with increased prevalence of micro- and macro-albuminuria compared to patients without persistent LVH on ECG.
Once formed, an addiction can be a life-long condition in which individuals show intense drug craving and increased risk for relapse after years and even decades of abstinence [125].
This means that addiction involves extremely stable changes in the brain that are responsible for these long-lived behavioral abnormalities [125]. Hyperglycemia and insulin resistance as risk factors of cardiovascular complications in type 2 diabetesHyperglycemia and hyperinsulinemia or insulin resistance that is a characteristic of type 2 diabetes and obesity play major roles in the cardiovascular complications of type 2 diabetes mellitus and obesity. The hypothesis of obesity treating as an analogy of drug addiction is supported by evidence for a food addiction diagnosis according to the Yale Food Addiction Scales [127-129] and fMRI in humans [92]. Hyperglycemia is the major risk factor for microvascular complications (retinopathy, neuropathy, and nephropathy) in type 2 diabetes, however 70% or 80% of patients with type 2 diabetes die of macrovascular disease. Atherogenic dyslipidemia (elevated triglyceride levels, low HDL-cholesterol levels, high LDL-cholesterol levels) is the major cause of atherosclerosis in patients with type 2 diabetes [Reasner, et al. Such questionnaires include the “3Cs” of addiction, compulsive use, attempts to cut down, continued use despite consequences, among others [127]. 2008].Several investigators have demonstrated that insulin resistance could predict future type 2 diabetes even in nonobese individuals [Morrison, et al.
The most common symptoms were (1) persistent desire or repeated unsuccessful attempts to cut down, (2) continued use despite problems, and (3) much time spent to obtain food, eat, or recover from eating [127].
Meule et al reported that prevalence of food addiction diagnoses differed between weight classes such that overweight and obese participants had higher prevalence than normal weight participants [Figure 6; 128]. These “compulsive food consumption” is difficult to modify, and even if weight loss is achieved, the neural plasticity “fixed” by palatable food leads individuals to crave palatable food and thus substantially regain weight. 2008] Insulin resistance accompanying sympathetic nerve activation may also predict future hypertension development [Masuo, et al. Insulin resistance coexisting with inflammation may predict cardiac disease but, interestingly, not stroke in the Japanese diabetic population [Matsumoto, et al.
Also, from the finding that obese patients have been shown to have decreased D2 receptor level in striatum by positron emission tomography (PET) imaging, obesity has been described as a reward deficiency syndrome, where deficiency of dopamine signaling results in compensatory over eating [105, 125].
It is not known that these functional changes are the results of obesity or the cause of obesity. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight reduction and cardiovascular risk factors in overweight patients: 1-year experience form the RIO-Europe study.
Sympathetic nervous activity as a risk factor for cardiovascular complications and renal complicationsHeightened sympathetic nerve activity plays an important role in cardiovascular complications and cardiac risk in humans [Esler, et al. There is consistent evidence that high plasma norepinephrine level, as an index of heightened sympathetic nerve activity, predicts mortality in cardiovascular diseases such as chronic congestive heart failure [Cohn et al. Efficacy and tolerability of rimonabant in overweight or obese patient with type 2 diabetes: a randomised controlled study. 2010], structural changes in obesity {Benedict, 1996}, and end-stage renal disease (ESRD) [Masuo, et al. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials.
Stress affects feeding behavior in humans in both directions, with some individuals increasing their food intake while others eat less [131]. An overall increased consumption of caloric dense and highly palatable foods following stress compared to non-stressed controls is reported, independent of stress-induced hyperphagia or hypephagia [131]. Susceptibility to stress and stress-induced hyperphagia are observed in obese individuals [132]. Depression, other mood disorders, and cognitive impairment also affect the feeding behavior of obese individuals.
Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control.
2001] reported that acute myocardial infarction (AMI) in hypertensive patients resulted in greater sympathetic nervous activity, persisting for at least 6 months longer than in normotensive subjects, indicating that AMI further augmented the sympathetic nerve hyperactivity of hypertension.
Sympathetic nerve hyperactivity could be one mechanism involved in the reported worse prognosis in AMI in hypertensive patients [Hogarth, et al.
LeptinLeptin is one of the most important adipocyte-derived hormones and circulate in proportion to body fat mass, enter the brain, and act on neurocircuit that govern food intake and energy expenditure [124]. Malmberg K, Ryden L, Wedel H, Birkeland K, Bootsma A, Dickstein K, et al; DIGAMI 2 Investigators. The long form of the leptin receptor (Ob-Rb) expresses in numerous regions including the hypothalamus, VTA, and NAc. The sympathetic activation that follows AMI has been associated with increased morbidity and mortality in both anterior-AMI and inferior-AMI, with a similar magnitude of sympathetic nerve hyperactivity [Graham, et al.
Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Through both direct and indirect actions, leptin diminishes perception of food reward (the palatability of food) while enhancing the response to satiety signals generated during food consumption that inhibit feeding and lead to meal termination [124]. Human adipose tissue expresses angiotensinogen and enzymes required for its conversion to angiotensin II. Administrations of leptin in the VTA directly regulate mesolimbic dopamine system [134-135].
Patients with congenital long-QT syndrome are susceptible to life-threatening arrhythmias, and the sympathetic nervous system may have an important triggering role for cardiovascular events this condition [Shamsuzzaman, et al.
Centrally administered leptin diminishes both sucrose preference and the effect of fasting to increase the rewarding properties of electrical pleasure-center stimulation [136-137].
2001].Changes in heart rates during exercise and recovery from exercise are mediated by the balance between sympathetic and vagal activity, and changes in heart rates were evaluated in a total of 5,713 asymptomatic working men cohort (between the ages of 42 and 53 years) in whom there was no evidence of the presence or history of cardiac disease over the preceding 23 years. The effect of weight loss to lower leptin levels and hence to reduce leptin signaling increases rewarding properties of food while diminishing satiety, a combination that potently increases food intake [124].
Baseline heart rates, changes in heart rates during exercise and recovery were strongly related to an increased risk of sudden death from myocardial infarction [Jeuven, et al. GhrelinGhrelin is recognized as the only known orexigenic peptide hormone and synthesized mainly by a distinct group of endocrine cells located within the gastric oxyntic mucosa [136].
Papel de la angiotensina II producida en el adipocito en el desarrollo del sindrome metabolico.
The mechanisms by which ghrelin promotes food intake are multifaceted and include not only stimulating intake of food via homeostatic mechanisms but also enhancing the rewarding properties of pleasurable food [139-140]. 2002 & 2004] examined the relationships between sympathetic nerve activity (plasma norepinephrine levels) and mortality and cardiovascular events in 228 patients undergoing chronic hemodialysis originally without heart failure. Ghrelin can directly affect dopaminergic VTA neuronal activity and increase motivational aspect of reward [139].
They found 45% of dialysis subjects had significantly high plasma norepinephrine levels located in the upper limit of the normal range.
Intra-VTA administration of ghrelin modulates intake of freely available regular chow, food preference, motivated food reward behavior, and increases body weight [139].
One-hundred and twenty four (124) fatal and nonfatal cardiovascular events occurred in 85 patients during the follow-up period (34±15 months).
Plasma norepinephrine levels proved to be an independent predictor of fatal and nonfatal cardiovascular events in a multivariate Cox regression model.
InsulinInsulin is produced by pancreatic ?-cells, controls plasma glucose levels, increases in proportion to fat mass, consequently relay information about peripheral fat stores to central effectors in the hypothalamus to modify food intake and energy expenditure.
Neurons in the ARC of the hypothalamus express insulin receptors and regulate energy homeostasis. The receptors for insulin are also present in brain reward circuitry, which are thought to be projected from LH in the hypothalamus [126, 142-143]. Insulin works as satiety hormone similar to leptin, and also attenuates food reward similar to leptin, substantially suppresses food intake [126, 144].
Insulin signaling and dopamine signaling via dopamine 2 receptor (D2R) work in tandem to regulate dopamine transporter plasma membrane expression and function [145]. They also found that plasma norepinephrine levels were associated with concentric left ventricular hypertrophy in these patients [Zoccali, et al. Brain insulin resistance which is often accompanied with obesity also exists in brain regions regulating appetite and reward [146].
Dysregulation of brain insulin signaling might alter dopamine reward pathways resulting in changing motivation for food since these pathways are insulin sensitive [145].
Jastreboff et al demonstrated a fMRI study that in obese individuals, food craving, insulin, and HOMA-IR levels correlated positively with neural activity in corticolimbic-striatal brain regions including the striatum, insula, and thalamus during favorite-food and stress cues [147].
2002] showed that increased cardiac sympathetic nervous activity in renovascular hypertension might lead to high cardiovascular mortality and morbidity. Prolonged sympathetic nerve stimulation and elevated circulating norepinephrine levels can induce changes in intra-renal blood vessels. Catecholamines can induce proliferation of smooth muscle cells and adventitial fibroblasts in vascular wall.The association between hypertension, obesity and chronic kidney disease (CKD) is well recognized [White, et al. In the majority of cases, ESRD occurs as a result of complication of diabetes or hypertension [WHO. Obesity, hypertension and type 2 diabetes are characterized as stimulated sympathetic nervous activity and insulin resistance states, indicating renal injury and ESRD are strongly related to sympathetic nervous activity and insulin resistance. The findings suggest that strong linkage between sympathetic nervous activity, insulin resistance and renal function. The 40-minute infusion of NE into the renal artery of dogs produced a reversible ischemic model of acute renal failure [Bulger, et al. Another study demonstrated renal protection by ?-adrenergic receptor blockade in a nephrectomized rat experiment without any BP changes [Amam, et al.
There is consistent evidence that high plasma norepinephrine levels, as an index of heightened sympathetic nervous activity, predicts mortality in cardiovascular disease, such as chronic congestive heart failure [Cohn, et al. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the US.
These investigations have shown strong associations between sympathetic nervous activation, cardiovascular complications and renal complications.
Sympathetic nerve hyperactivity in patients with ESRDEvidence now strongly indicates a role for the sympathetic nervous system in the pathogenesis of hypertension in renal failure (ESRD) [Hausberg, et al.
Socioeconomic, cultural, and personal influences on health outcomes in low income Mexicanorigin individuals in Texas.
Hypertension occurs commonly and early in renal disease and is paralleled by increases in sympathetic nerve activity, as indicated by increased muscle sympathetic nerve activity and circulating norepinephrine.
This appears to be driven by the diseased kidneys, because nephrectomy or denervation has been shown to correct blood pressure and sympathetic nerve activity both in human and animal studies [Jacob, et al. The importance of waist circumference in the definition of metabolic syndrome: prospective analyses of mortality in men.
1995 & 2010] showed that plasma norepinephrine levels were significantly higher in patients with ESRD regardless of hemodialysis compared with those in blood pressure- and body mass index-matched hypertensive patients or healthy normotensive subjects (Figure 3).
Further, this was recognized significantly in subjects with a shorter duration of ESRD with hemodialysis compared with those with longer duration, suggesting that sympathetic nerve hyperactivity may be of particular importance in the onset or the early development of ESRD or, alternatively, be influenced by long-term renal replacement therapy (hemodialysis). In the normal state, interactions between the kidney and sympathetic nervous system serve to maintain blood pressure and glomerular filtration rate within tightly controlled levels, but in renal failure, a defect in renal sodium excretory function leads to an abnormal pressure natriuresis relationship and activation of the renin-angiotensin system (RAS), contributing to the development of hypertension and progression of kidney disease [Hall, et al.
Does the new International Diabetes Federation definition of the metabolic syndrome predict CHD any more strongly than older definitions?
Another mechanism could involve the sympathetic nervous modulation of baroreflex regulation and vasculature tone through the central nervous system and angiotensin II [Burke, et al. Afferent signals from the kidney, detected by chemoreceptors and mechanoreceptors, feed directly into central nuclei regulating sympathetic nerve activity by circulating and brain-derived angiotensin II [Philips, et al. Preventing pregnancy induced hypertension: are there regional differences for this global problem?
Therefore, the pathogenesis of hypertension in renal failure (ESRD) is complex and arises most likely from the interaction of hemodynamic and neuroendocrine factors. Sympathetic nerve activity has strong relationships with regards to increased risk of cardiovascular disease including hypertension [Zoccali, et al. The sympathetic nerve hyperactivity is at least in part independent of increased blood pressure levels or obesity.
Further, patients with early-ESRD without hemodialysis had already significantly higher plasma norepinephrine levels compared with hypertensive subjects as well as normotensive subjects. Therefore, sympathetic nervous activation in ESRD patients may be independent from obesity or hypertension. In addition, plasma norepinephrine levels did not change between before- and after-hemodialysis therapy (data was not shown), and between after-hemodialysis therapy and before-next hemodialysis therapy.
Thus, one could speculate that plasma norepinephrine levels in ESRD patients are reflective of the degree of sympathetic nerve activity.
?2-adrenoceptor polymorphisms accompanying sympathetic nervous activation may relate to renal injury Rao et al. 2007] have shown strong associations between ?2-adrenoceptor polymorphisms, elevated plasma norepinephrine levels and elevated HOMA-IR (insulin resistance) or future renal injury, suggesting that stimulated sympathetic nerve activity associated with insulin resistance, may independently play a major role in the onset and development of ESRD without obesity or hypertension.
However, the precise mechanisms underlying sympathetic activation in CKD and ESRD have not been clarified.Furthermore, Masuo et al.
2011b] measured renal function (creatinine, BUN and creatinine clearance), plasma norepinephrine levels and HOMA-IR (insulin sensitivity) annually over a 5-year period in nonobese, normotensive men with normal renal function.
Subjects who had a significant deterioration of renal function (more than 10% increases from baseline of creatinine and BUN or decrease in creatinine clearance) over a 5-year period had higher plasma norepinephrine at the entry period, and greater increases in plasma norepinephrine over 5 years [Masuo, et al. In this study, subjects who had significant changes in body weight or blood pressure were excluded, indicating the contributions of obesity or hypertension might be excluded. Further, subjects who had significantly higher levels of plasma norepinephrine had a higher frequency of the Gly16 allele of the ?2-adrenoceptor polymorphism [Masuo, et al. The Gly16 allele of the ?2-adrenoceptor polymorphism has been shown to be related to obesity [, Masuo, et al. Thus, high plasma norepinephrine levels appear to be a predictor that is determined genetically by the ?2-adrenoceptor polymorphism (Arg16Gly) for renal injury, obesity, hypertension and metabolic syndrome.In 154 nonobese, normotensive subjects, renal function (creatinine clearance) was measured over a 5-year period. The deterioration of renal function was defined as >10% decreases in creatinine clearance over a 5-year period. Subjects with deterioration of renal function had higher frequency of Gly allele or Gly homozygous compared to those without changes in renal function. Obstructive sleep apnea in obesity is a risk factor for cardiovascular diseasesVozoris [Vozoris. 2012] investigated the relationships between prevalence of obstructive sleep apnea (OSA), obesity, and hypertension, diabetes, congestive heart failure, myocardial infarction, and stroke using a population-based multi-year cross-sectional study design including 12,593 individuals with data from the 2005-2008 United States National Health and Nutrition Examination Surveys (NHANES). Calcium supplementation reduces the risk of pregnancy-induced hypertension in an Andes population.
They found individuals with OSA had elevated rates of cardiovascular diseases compared to the general population [Vozoris. OSA is a common disorder that has been associated with many cardiovascular disease processes, including hypertension and arrhythmias.
OSA has also been identified as an independent risk factor for stroke and all-cause mortality. OSA is highly prevalent in patients with transient ischemic attacks and stroke [Das, et al. The mechanisms underlying the link between OSA and cardiovascular disease are not completely established. Prevention of preeclampsia with calcium supplementation and its relation with the L-arginine:nitric oxide pathway. A number of studies have consistently shown that patients with OSA have high levels of sympathetic nerve traffic [Narkiewicz, et al.
In animal studies, intermittent hypoxia that simulates changes seen in OSA leads to chemoreceptor and chromaffin cell stimulation of sympathetic nerve activity, endothelial damage and impaired blood pressure modulation. Human studies reveal activation of sympathetic nerves, endothelial damage and exaggerated pressor responses to sympathetic neurotransmitters and endothelin [Ziegler, et al. Endothelial NO synthase genotype and risk of preeclampsia: a multicenter case-control study. Gout and hyperuricacidemia in obesityGout is a growing worldwide health problem, and is associated with increased prevalence of obesity. Plasma concentrations of asymmetric dimethylarginine (ADMA) in Colombian women with pre-eclampsia.
Gout and hyperuricacidemia are associated with the metabolic syndrome, diabetes mellitus, obesity and hypertension. Several epidemiological studies have shown the close linkage between hyperuricemia, obesity and hypertension [Robinson, et al. 2012] reviewed prevalence of hyperuricemia in Australia in 25 articles and 5 reports using a systematic journal search method.
Similar result has been reported in Taiwanese populations that, using a multivariate analysis, showed that BMI (obesity) was an important factor associated with hyperuricemia in both males and females, whereas age was associated with hyperuricemia only in males. In addition, the associations of basic and repeated measures of uric acid level with treatments for uric acid over a 11-year period, and risk of coronary heart disease (CHD) and stroke events were assessed in Taiwanese populations [Chien, et al. The study showed that uric acid had significant risk only in hypertension and metabolic syndrome subgroups, but not in their counterparts.
They also observed that uric acid, in the baseline and time-dependent variables, could predict cardiovascular events in the community of relatively low CHD but high stroke risk. Romero-Corral A, Somers VK, Sierra-Johnson J, Thomas RJ, Collazo-Clavell ML, Korinek J, et al. Furthermore, they compared these effects between a mild calorie restricted diet alone, combination with a low calorie diet and exercise and control groups. Interestingly, moderate weight loss in obese patients with metabolic syndrome is associated with a reduction in serum uric acid levels, albuminuria and an improvement in eGFR which is augmented by exercise co-intervention [Straznicky, et al.
Improvement of insulin resistance and sympathetic activation were synchronized with a reduction in serum uric acid levels. ConclusionThe role of the sympathetic nervous activity and insulin resistance plays important roles in the etiology of obesity, hypertension, and type 2 diabetes.
Several investigations have demonstrated that the sympathetic nervous activation and insulin resistance are strongly related to cardiovascular complication (i.e.
Interestingly, relevant investigations of sympathetic nervous activity and ?2-adrenoceptor polymorphisms indicate their contribution to the onset and maintenance of renal injury and LVH in healthy subjects and in patients with chronic renal failure and cardiovascular events in ESRD patients. Interestingly, the prevalence of OSA and hyperuricemia (gout) are significantly linked with increases in obesity, and both states are connected with the cardiovascular risks associated with sympathetic nervous activation. Serum uric acid, which may be affected strongly by sympathetic nervous activity, may be a predictor for future hypertension and renal injury (ESRD) development. Recently, it has been demonstrated that renal sympathetic nerve denervation provides promising results in patients with refractory hypertension [Krum, et al. Besides the demonstrable effect on reducing blood pressure, renal denervation significantly and favourably influences LV mass and improves diastolic function, which might have important prognostic implications in patients with resistant hypertension at high cardiovascular risk [Brandt, et al. Further, renal denervations showed an accompanying improvements in insulin resistance [Mahfoud, et al. Renal sympathetic denervation may conceivably be a potentially useful option for patients with co-morbid refractory hypertension, glucose intolerance, and obstructive sleep apnea.A better understanding of the relationships between sympathetic nervous activity, insulin resistance, cardiovascular complications, and renal complications, will help to develop appropriate treatment strategies targeting renal injury or cardiac risk in hypertensive and diabetes patients with and without ESRD or LVH. Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E, Obesity Canada Clinical Practice Guidelines Expert Panel.



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