Biology of Obesity and Energy Homeostasis

The incidence of obesity has become a major health issue that is barely unrecognized in every medical journal. Despite widely researched works on the pathogenesis of obesity, it is rather unfortunate that it remains a life-threatening health risk in susceptible individuals. The onset of obesity is gradual in form and arises from daily accumulation of fat in adipose tissues in excess of body anabolic needs (building up process). One can trace fat storage in humans to the adaptive need for energy conservation until when needed. Fat is stored in order to serve as source of energy for later breakdown in scarce resources. This is a body physiological response toward maintaining a perfect homeostatic environment. Homeostasis allows body to remain energized even in the absence of immediate food for ingestion within bearable length of time. However, due to inherent physiologic conditions, mutations in regulatory systems of peptideshormones and bad eating habit, some are more vulnerable to excessive fat accumulation thus leading to obesity. Scientifically, obesity occurs when the Body Mass Index (BMI) for an individual exceeds the limit of standard in relation to persons height and body weight. A body mass index exceeding or equals 30kgm2 gives rise to objective assessment of the condition known as obesity in an individual. BMI below this limit is overweight i.e. 25 kgm2 to 29 kgm2. The normal level of body mass index ranges between 19 kgm2 and 24 kgm2.

There are cellular regulators of fat storage in the body. The regulators signal when fat storage is in excess and stop further process of accumulation. Obese individuals have weak feedback signals wherein a loss of minimum weight already signals extreme hunger that makes these subjects respond by eating immeasurably more than body needs. The etiology of obesity and imbalance control of energy homeostasis is traceable to both hereditary and environmental factors. The central signal that allows for body regulation of fat lies within the first part of the Central Nervous System called the brain. Being that glucose supplies the ATP requirements for brain function, brain in turn acts in response to feedback sensation of hypoglycemia (reduced blood glucose) and hyperglycemia (excessive blood glucose) in order to normalize the concentration of glucose in body circulation. It is important to note that an increase in glucose level promotes prompt release of insulin by the pancreas to convert excess glucose into storable glycogen and complex chains of triglycerides. The liver starts to decrease release of glucose in this situation. Conversely, when there is insufficient glucose and the body drives towards exhaustion of energy, fat cells release triglycerides into the bloodstream for compensation.

Certain hormones in body mechanisms regulate fat production, usage and storage. Leptin is one hormone that signals excessive amount of fat in the body thereby promoting decrease in appetite (Flier  Maratos-Flier, Sep2007). In this case, increases in weight problems are due to the mechanisms of our body malfunction and switch away from this stabilization system. This could be due to mutation in the production of leptin or mutation of the leptin receptors thereby causing abnormal response or no response.

Energy homeostasis is the process involving series of molecular signals, wherein body environment constantly balances between food intakes with energy need. Despite unguided consumption that is not proportionate to energy requirements in our body, the center of appetite regulation in the brain adjusts gastrointestinal systems of body metabolism accordingly to ensure homeostasis. Certain system malfunctions and overwhelming of existing homeostatic system tend the body towards obesity. This paper will explore the role of gastrointestinal system we shall equally take into consideration the different chemicals and hormones involved in the maintenance of body weight. With the discovery of these mechanisms, diseases that threaten life such as diabetes and obesity might further receive expert understanding for possible way out of obesity scourge.

The Digestive System
The digestive system of the body is responsible for the break-down of the food we take eat, making it absorbable for different organs of body system to function properly. The product of digestion is molecular and soluble in such a way that it is deliverable through micro and macro vasculatures of the body. Digestive organs include the mouth, Pharynx, Esophagus, Stomach, Large Intestine, Small Intestine, Rectum and Anus. These organs together with accessory organs contain cellular and molecular system of controls that regulate nutrition and energy consumption. Digestive system accessory organs include Salivary glands, Liver, Gall bladder and Liver.

Meanwhile, mouth is the first part of digestive system where functions include enzyme digestion and mastication. In mastication, there is mechanical grinding of food particles in order to pass through the esophagus without obstruction. The food then passes thereafter to the pharynx, from the pharynx to the esophagus and into the stomach. The stomach mixes the food with stomach juices and regulates the entry into the small intestine. Movement takes place into the small intestine after which the food proceeds to the large intestine for further digestion and eventual exit through the anus. Several enzymes break down the food depending on its composition and location along the gastrointestinal tract. The primary digestive enzymes for respective food nutrient include amylase for carbohydrates, lipase for fats and proteases for proteins.

Regulation of Food Intake
Satiation is the term used to describe the regulation of food consumption. The feeling of fullness during complete satisfaction explains the concept of this process. Signals sent by the brain to achieve stoppage of food intake further explain this concept. The process serves as food consumption control and helps prevent consequences related to overeating one consequence is dyspepsia. How does this work The hindbrain is responsible for the reception of satiation signals arising from the areas in the gastrointestinal system especially the stomach.

Gastrointestinal peptides that regulate food intake but not produced in the brain are leptin, insulin, glucagons and amylin. CCK, APO AIV, GLP1, oxyntomodulin, PYY, enterostatin, ghrelin, GRP, neuromedin-B and PP. These molecules present in abundant in the digestive tract are peptides regulating digestion and controlling food appetite through molecular networks of mediating factors. The liver and the gall bladder also make vital contribution in the absorption water insoluble vitamins and fats.  Excessive secretion of peptides and other factors lead to over absorption of digested food from the small intestine and large intestine (primary site of absorption) thus precipitating obesity.

Satiation Signals by the Gastric gland
 The stomach structure contains a number of rugae that expands during eating. However, it only expands to certain limit. Experiments had shown that control of pyloric sphincter at the exit of the stomach is chemical-mediated by gastric gland in that through signal response, it contracts and relaxes, thus, opens to allow food passage to small and large intestines. Through this rhythmic action, pyloric sphincter has its role in satiation process. The closure of the pylorus terminates ingestion in of food. In addition, the depletion of energy will promote ingestion, and food will move downward for the nutrients to be absorbed in the small intestines. For the pyloric sphincter to close, a certain amount of ingested food is required. However, 40 of ingested food emptied into the intestine is required, before the pylorus can close. This proves that the pre-gastric, gastric and intestinal signals function all together to regulate food intake.

In relation to the ingestion of food, glutamate, acetylcholine, nitric oxide, calcitonin-gene-related peptide, substance P, galanin, and cocaine-and-amphetamine-related transcript are the neurotransmitters that send signals to the brain. With the framework of mechanoreceptors present in the stomach endothelium, appropriate responses signal to control satiation and stomach fullness. Examples of signals-related mechanoreceptors are sensors of tension, stretch and volume.

Another example of peptides found in the stomach is the bombesin-related peptides, gastrin-releasing peptide, and neuromedin B. The gastric myenteric neurons produce these substances, and scientific studies found out that they could reduce food consumption when there is satiation in order to achieve energy balance or homeostasis.

Satiation by the Intestines
Unlike gastric satiation that depends on volume for its satiation, intestines satiate in physiologic response to nutrient absorption. It stops absorption when they have absorbed sufficient nutrition required by the body system. Studies also found out that Cholecystokinin is the primary peptide responsible for intestinal satiation. The effect of intestinal satiation is again on the prevention of excessive food intake. Through this system, there is achievement of energy homeostasis and prevention of obesity.

Cholecystokinin from I-cells is located in the duodenal mucosa, jejuna mucosa of the upper intestines, brain and the enteric complex of nerve cells. In response to ingestion of excess amounts of proteins and lipids, body releases Cholecystokinin to hinder further food intake and ensure energy balancehomeostasis. This type of satiation specifically the carboxy-terminal octapeptide group of the CCK does not affect water intake that can cause dehydration, it is only specific for the regulation of nutrient intake and absorption.

Complementary to the upper intestinal satiation is the lower intestinal satiation that involves the secretion of GLP1 by L-cells located in the distal small intestine and colon. Satiation through GLP 1 occurs by preventing food motility in the gastrointestinal tract as well as gastric emptying as a mechanism to regulate food consumption. Many doctors already use GLP1 to treat patient with diabetes. This has shown to be effective as patients lost considerable weight following ingestion of drug containing GLP1 chemical.

Furthermore, oxymontomodulin and PYY are another peptides involved in satiation specifically in the lower intestine. Studies also found out that Oxyntomodulin decreases food intake, especially in rodents. In humans, it decreases the feeling of hunger and controls obesity without leaving out the maintenance of energy homeostasis.  Satiation peptides specific for fats
 Enterostatin and apolipoprotein A-IV are peptides specifically involved in fat satiation. For enterostatin, the mechanism behind control of satiation is due to F1-ATPase  subunit that serves as blocking receptor, thus controlling absorption. Through expert studies, enterostatin showed no effect on human regarding food intake restriction through appetite reduction. However, same study discovered that APO A-IV decreases food consumption.

We have seen how chemicals-mediated satiation process controls excessive weight gain by preventing food overload and maintains energy homeostasis. Specific satiation peptides involve in the regulation of food consumption especially fatty and carbohydrate substances that mostly lead to obesity due to ability of the body to conserve them for future need. It is a strongly believe that further research works in the subject of regulatory satiation process will open more scientific understanding on the subject and the consequential outcome of the research will solve the struggle on obesity and energy homeostasis in the field of internal medicine. The future is brighter


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