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In this multi-part series I hope to start unraveling the science behind the phenomenon we call weight loss. The question, “So why do we get fat in the first place?” seems like a logical place to begin.
Some maintain that the principle cause of obesity, which is the symptom we’re discussing, is fat de-regulation.
In this context, physiological factors refer to homeostatic mechanisms, hormones and their effects, as well as how our body’s machinery deals with food’s specific constituents or macronutrients. The stomach also functions to churn and mix the bolus into a consistency known as chyme, or partially digested food.
The small intestine also continues the digestive process by using additional enzymes to further digest proteins, carbohydrates, and fats as well as further mixing the chyme.
For the sake of completeness in the digestive system path, we finish up our discussion with the large intestine. The hypothalamus an almond-sized portion of the brain that lies in the midline of the human brain at the level of the eyes approximately. There are five main hormones that stimulate appetite, hunger, and feeding and they are as follows: ghrelin, agouti-related protein, neuropeptide Y, melanin concentrating hormone, and anandamide. After a period of fasting, like the time between meals or when you sleep overnight, ghrelin is secreted from cells in the stomach into the bloodstream where it makes its way across the blood-brain barrier to act on certain cells in the hypothalamus. When satiety occurs, leptin, which is made by fat cells (adipocytes), activates the previously inhibited POMC cells to release appetite suppressants alpha-melanin stimulating hormone and beta endorphin, respectively, which act upon the same cells in the hypothalamus that initiated the feeding. Ghrelin, as mentioned before is made by cells in the stomach and released in the bloodstream in ever-increasing amounts before meals. Look for the rest of the hormones, their practical applications, and further discussion on the psychological influence on obesity in the upcoming parts!
The material on this web site is provided for educational purposes only, and is not to be used for medical advice, diagnosis or treatment.
My hope is that through an understanding of the mechanisms responsible for obesity and body-fat accumulation as well as body-fat loss and leanness, we will be able to target the causative agents behind the physical appearance. However, it is wrought with confounding variables that don’t allow for a single causative element to be identified. In other words, obesity is not the disease, but rather the symptom in a series of other comorbidities (multiple disorders being present) that is caused by an improper regulation of the fat tissue itself. Let’s begin with the digestive process and the subsequent hormonal, physical, and mechanical changes. Digestion is both the mechanical and chemical breakdown of a food or meal into smaller products that only then can be absorbed. In anatomy, things that pertain to the stomach generally have the word gastric included in the nomenclature. Proteins are now broken down into peptides and amino acids, carbohydrates are broken down into glucose mainly, and fats are broken down into fatty acids and glycerol products.
This part of the digestive system is about five feet long and consists of the cecum, colon (ascending, transverse, descending, and sigmoid divisions), and rectum. It is connected to the pituitary gland via a stalk, the infundibulum, and is responsible for many different processes including hunger. The appetite suppressing hormones include the following: leptin, alpha-melanin stimulating hormone*, beta endorphin,  cholecystokinin (CCK), incretins, insulin, amylin, pancreatic polypeptide, peptide YY (PYY), and brain-derived neurotrophic factor (BDNF). However, a few cases of extreme obesity have been traced to mutations in the brain receptor for alpha-melanin stimulating hormone, which may be acted upon by this hormone produced by melanin synthesizing skin cells in response to UV light.


These cells are now activated and go on to stimulate agouti-related protein and neuropeptide Y releasing cells, both of which can be found in the hypothalamus. This stimulation by these specific hormones on these specific cells in the hypothalamus continues until feeding is stopped. The longer one goes between meals, the more ghrelin will be released and the more stimulation there will be for hunger.
In order to post comments, please make sure JavaScript and Cookies are enabled, and reload the page. I’d like to propose that this is an aerial shot of the whole issue, a large-scale view of obesity, if you will. When we take a bite of food and it enters into our mouth, we use our teeth to mechanically break down the food into smaller chunks.
For instance, the enzymes released in the stomach are referred to as gastric enzymes.  There are five main enzymes released in the stomach that are produced by four cell types within the organ, of which each has a specific purpose.
The small intestine is broken up as follows from most proximal to distal: duodenum, jejunum, and ileum. Now we know how our macronutrients, protein, carbohydrates, and fats, are broken down in the body! It is important, in my opinion, to figure out why we eat in the first place and then discuss the hormonal changes that occur in lieu of the feeding.
There are clusters of cell bodies (nuclei) in various parts of the hypothalamus that have been shown to regulate feeding, satiety, hunger, and other processes related to eating and metabolism. A mutation in this receptor may render them unable to respond to its appetite-suppressing effects. This cascade is important however, so I suggest you read through that a few times and do some Googling to make sure you’ve got it. Bacteria normally found in the intestines build up and make toxins in the lining of the appendix. The remainder of this series will describe why someone gets fat in the first place, specific targets for intelligent interventions to facilitate fat loss, and current theories in the fat loss game. Conversely, other scientists and media persons have focused on individual hormones (insulin, leptin, neuropeptide Y, adiponectin, etc.) and their purported effects on body fat mass. In addition, an enzyme known as salivary amylase is secreted into the oral cavity to initiate the breakdown of certain starches into smaller units, usually maltose. At this point absorption of the digested food begins, which is where the hormonal fun continues.
Within the large intestine there is also a preponderance of bacterium, or gut flora that is commensal, or beneficial in humans. In short, the hypothalamus is part of the brain (central nervous system), and as such, it receives input from the periphery of the body via various hormones and signals that cross the blood-brain barrier (BBB) and act upon it. We’ll continue on by going in depth with all the hormones as well as using some practical examples to get the point across.
I refer to this as a ground-level view of obesity and in my opinion; this can lead to a “missing the forest amongst the trees” sort of effect.
No food has yet been absorbed at this point, however insulin levels have already increased in what’s known as the pre-absorptive insulin response or cephalic insulin response. Parietal cells produce hydrochloric acid and intrinsic factor, which are responsible for protein breakdown and bacteria or virus destruction and absorption of vitamin B-12, respectively. It has small finger like projections called villi that project inside the tube and each villi has even smaller projections called microvilli that are covered with cells (enterocytes).


Remember, we already had a cephalic insulin response that occurred upon eating some time ago and only now are we getting ready to see some real hormonal changes. These bacteria metabolize certain constituents of the chyme and produce various byproducts that we absorb and need as well as prevent infection if everything is going well down there. We can subdivide the important hormones into either appetite stimulating or appetite suppressing categories.
I maintain, as do most intelligent people involved in this field, that the cause(s) of obesity, fat accumulation, and the preponderance of people who lose weight to gain it back, is multifactorial in nature. This insulin response can be considered to be hardwired, as it occurs no matter what to deal with the impending blood sugar increase. Chief cells produce pepsinogen, which when activated breaks down protein into peptides and amino acids. The villi and microvilli both serve the small intestine to increase its surface area for absorption of the digested nutrients. Vitamin K, vitamin b12, thiamine, and riboflavin are all examples of bacterial products that we utilize for normal functions. I can sum all the causative elements of fat gain to the following two categories: psychological factors and physiological factors. Whether or not that actually occurs (the blood sugar increase) however, is dependent on what the meal consists of and a multitude of other factors that we’ll cover later. G-cells produce a hormone called gastrin in response to food entering the stomach and stretching it. Over ten trillion colonies of bacteria from the bacteriocide, lactic, enterica, enterococci, clostridia, and methanogen groups are present. I understand that using these categories results in a blanket, broad stroke approach to understanding obesity, however since it is multifactorial I feel okay about doing this.
The food is now also called a bolus, and will now continue it’s transmission through the gastro-intestinal tract. The differences in flora composition are influenced by age, diet, cultural considerations, and antibiotic usage, where each person’s gut flora is even more individualized than their fingerprint.
Last but not least, we have goblet cells, which produce mucin (mucous) and bicarbonate that neutralize the acidic environment of the stomach slightly, so as to preserve the lining of the stomach to a degree. Current ground-breaking research is taking place on certain bacteria concentrations and in the gut and their effect on health.
All this is to show you that there are tons of things happening on a physiological level within each organ the food passes through and we haven’t even begun to absorb any of the nutrients yet! After the vitamins, minerals, and water has been extracted from the digested food the remainder is compacted and stored as feces until elimination. Another takeaway from this is that digestion of carbohydrates begins in the mouth, whereas digestion of proteins begins in the stomach. Fats have not yet been digested at all, and none of the macronutrients have actually been absorbed.



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