The mechanisms involved with the regulation of food intake in the body, mainly feature the combined work of the brain, the adipose tissues, and the gut, among the top organs. Systems such as sympathetic, and parasympathetic among others, are also necessary for proper communication between the brain and satiety center, the adipose tissue, and the gut.
Think of these as neuronal circuits that also feature a variety of hormones and chains of amino acids, as well as other appetite inhibitors – a clear indication of the importance of physiology when it comes to the regulation of food intake and energy homeostasis in the human body.
Nutrients obtained from food through the process of digestion are believed to be responsible for activating G-protein coupled receptors, but this is an activity that happens only in the luminal side of the enteroendocrine cells, such as the L-cells.
This action usually stimulates the gut to release natural amino acids and peptide hormones such as glucagon-like-peptide, peptide tyrosine, pancreatic polypeptide, and cholecystokinin into the circulation system. These are some of the hormones that are very well known to inhibit or suppress appetite, by making you feel satiated most of the time.
One of the peptides secreted from the stomach is ghrelin, and unlike most of the hormones produced by the gut system, its levels in the plasms are always known to decrease after the consumption of a meal. Insulin and leptin are other circulating factors that are responsible for relaying information about long-term energy stores.
The circulation of these two hormones is always in proportion to the body fat content, and they are also known to enter the central nervous system proportional to their plasma levels, hence, helping to reduce food intake.
It is believed that circulating hormones have the potential of influencing the functions of the arcuate nucleus neurons present in the hypothalamus section of the brain. It is also known that circulating factors such as gut hormones may also have an influence on the nucleus of the tractus solitarius via the neighboring circumventricular organ.
The arcuate nucleus, ARC, may sometimes work as an integrative center with two of the most important subpopulations of neurons responsible for influencing appetite, which usually leads to increased food intake. One of the subpopulations is Y and agouti-related protein – AgRP, while the other one is pro-opiomelanocortin (POMC).
Both are known to inhibit food intake, and can always project to areas that are responsible for regulating food intake, including regions such as the hypothalamic paraventricular nucleus, which normally receives important appetite information from other hypothalamic nuclei.
Below is a detailed look at some of the peptides at the core of food intake and digestion, as well as their specific functions of digestion.
Ghrelin is an orexigenic peptide that contains a total of 28 amino acids. The peptide is present in X/A-like cells – these cells are responsible for about 20% of all the cells within the endocrine cell population. Ghrelin-immunoreactive cells can also be found in places such as the colon, ileum, jejunum, and duodenum. The concentration of this hormone is known to decrease gradually as one moves from the duodenum towards the colon.
The peptide can also be secreted by other organs with the major ones being the pancreas and the hypothalamus sections of the brain. There are many factors known to regulate the production of ghrelin, and feeding is one of the best-known factors when it comes to the regulation of ghrelin. It has been noted that the concentration of plasma ghrelin usually spike during fasting, and will decrease upon food intake.
The specific factors that are responsible for this kind of regulation, however, are yet to be discovered. One of the highly suspect candidates, is the blood glucose level, hence, the administration of glucose may decrease the concentration of ghrelin in the plasma.
With the localization of ghrelin receptors on vagal afferent neurons in the rat ganglion cells, it is suggested that the hormone may be responsible for sending signals between the stomach and the brain through the vagus nerve. In short, the hormone is primarily produced in the stomach, as a response to starvation and hunger.
Once produced in the stomach in response to starvation and hunger, it then gets into the bloodstream where it works as a peripheral signal, communicating to the central nervous system through the vagus nerve, which then, stimulates feeding.
Neurons with ghrelin have also been found in the ARC of the hypothalamus – this is one of the regions responsible for regulating appetite. In some studies, it was observed that intracerebroventricular (ICV) injection of ghrelin leads to an overall increase in the cumulative food intake, and an overall decrease in energy expenditure. This led to an overall increase in body weight gain. For the stimulation of the release of the orexigenic peptides, neurons containing ghrelin has to send efferent fibers onto AgRP-expression neurons.
To reduce or suppress the release of orexigenic peptides, on the other hand, ghrelin-containing neurons must send fibers onto the POMC neurons. The ARC is usually a target of leptin – leptin is one of the leading appetite-suppressing hormones usually produced in the AT. Leptin has the ability to limit the appetite-stimulating effects of both AgRP and NPY.
Hypothalamic ghrelin, on the other hand, can prevent leptin-induced feeding. This is a subtle indication that leptin and ghrelin have a competitive nature of interaction when it comes to the regulation of feeding.
Ghrelin is just a hunger signal produced from the peripheral tissues. Subcutaneous and intravenous injections of ghrelin may therefore lead to an increase in food intake, while peripheral injection of the same may lead to the stimulation of the hypothalamic and ultimately lead to an increase in food intake. Since the rate at which the peripheral ghrelin goes through the BBB is very slow, peripheral ghrelin is necessary when it comes to the activation of the appropriate hypothalamic regions through yet to be identified indirect pathways.
Peptide tyrosine is another anorexigenic peptide that features 36 amino acids, several tyrosine residues, and it must have a c-terminal amidation for it to be biologically active. Low levels of PYY have always been recorded in the enteroendocrine cells present in the stomach, and these levels are known to increase proportionally as one moves towards the small and the large intestines, with the peak levels being realized at the colon and the rectum.
The L-cells present in the lining of the distal gastrointestinal tract is responsible for releasing PYY and this is usually done in accordance with the caloric intake. It has always been noted that the plasma levels of this peptide will usually go up within 30 minutes after the consumption of a meal.
It has also been observed that meals containing high levels of protein, usually lead to the greatest increase in levels of PYY, in comparison to other micronutrients. The anorectic properties of PYY seem to be regulated centrally through the ARC.
Pancreatic polypeptide – PP, contains a total of 36 amino acids that all belong to the PP-fold family of peptides. It is normally released post-prandially by the islet PP cells of the pancreas, but under vagal control. The peptide can be compared to other anorectic intestinal peptides like the PYY, which is usually secreted in proportion to caloric intake.
The pancreatic polypeptide has the ability to bind to all the members of the Y receptor family, though they are also known to have the highest affinity for the Y-4 receptor subtype. Some of the effects of the pancreatic polypeptide are believed to be influenced by the ventromedial hypothalamus, and the paraventricular hypothalamus parts of the brain. These two parts are vital when it comes to the control of appetite in the body.
This is a tetradecapeptide obtained from the skin of amphibians, and it shares a similar structure to mammalian gastrin-released peptide – GRP and neuromedin B. When bombestin is administered in conjunction with GRP, there is always a decrease in food intake in persons with normal weight, but the same is never the case with obese women.
When bombestin is administered peripherally or through central injection, it has the potential to reduce food intake that is not subject to being blocked by vagotomy. The peptide can also activate the sympathetic nervous system. In studies involving animals that have been starved, or those with ventromedial hypothalamic lesions, it was observed that the peptide could lead to a decline in temperature. This is because it is never possible to activate the sympathetic nervous system under such conditions.
Insulin is usually produced in the islet cells of the Langerhans present in the pancreas. Insulin usually accesses the brain through the blood circulation system acting through the hypothalamic neuron present in the ARC. There is also specific insulin transport available through the BBB. This is usually regulated by a saturable mechanism that features certain specific insulin receptors located in the brain’s microvessels.
The systematic injection of insulin or ICV infusion may sometimes result in a dose-dependent suppression of appetite and food intake in general. The central actions of insulin are also known to sometimes promote anorexia, since it usually decreases the expressions of both POMC and NPY.
Both leptin and insulin can activate POMC neurons, but their effects when it comes to regulating AgRP, seems to be different – leptin inhibits its synthesis, while insulin is known to stimulate the synthesis. A decrease in NPY usually leads to insulin deficiency, while the administration of insulin usually inhibits hypothalamic NPY expression.
Cholecystokinin – CCK, is also released post-prandially, but also from the small intestines. Studies show that it can co-localize with the PYY that are usually found in the L-cells. Its release is usually a response to saturated fats, amino acids, and other small peptides that are always a result of protein digestion. CCK2 receptors have also been recorded in peripheral tissues, with higher concentration being noticed in tissues such as the vagal afferent nerve fibers, gall bladder, and the pancreas.
Also, CCK1 receptors have been detected in certain areas where the central nervous system is involved with the regulation of food intakes such as in the dorsomedial hypothalamus, AP, and the NTS. CCK2 receptors, on the other hand, portrays a very different distribution.
They are present in the vagal afferent, hypothalamus, and gastric mucosa, among others. They have also been featured in several areas that are usually involved with the regulation of appetite. In human beings, the intravenous administration of CCK is known to reduce food intake and has also been shown to increase the perception of being full.
Oxyntomodulin is a peptide with a total of 37 amino acids. It is usually released post-prandially from the L-cells, with the amount released being proportional to the caloric intake. OXM is known to cause a reduction in some of the neuronal activities witnessed in regions such as PVN, and ARC, as well as the supraoptic nucleus.
This system of activation is known to be very different from that of GLP-1 when they are exposed to the same conditions. It simply means that these hormones work through different hypothalamus pathways. Oxyntomodulin may reduce food intake in persons with normal weight, and there is also evidence that it may increase energy expenditure in humans.
Amylin is a peptide with a total of 37 amino acids. It is also known as islet amyloid polypeptide. The peptide is usually co-released with insulin from pancreatic beta-cells in mammals as a response to food intake. The peptide seems to decrease food intake by using both peripheral and central mechanisms and, may, indirectly, slow down the process of gastric emptying.
The AP is known to play a very major role when it comes to the satiating effects of peripheral amylin. This usually comes with the direct activation of the AP neurons by blood-borne amylin. Its anorectic effects may sometimes be a result of the reduced expression of the orexigenic neuropeptides present in the LH area. Some studies have evidence that suggests that Amylin may also be able to express its effects through dopaminergic, histaminergic, and serotonergic systems.
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