See previous post: Obesity
Obesity is generally caused by consuming more than you need. However, the amount of body fat gained is not directly proportional to the amount of excess calories consumed. This phenomenon, known as "adaptive thermogenesis," may be due to a special kind of adipose tissue, called "brown fat."
Obesity is generally caused by consuming more than you need. However, the amount of body fat gained is not directly proportional to the amount of excess calories consumed. This phenomenon, known as "adaptive thermogenesis," may be due to a special kind of adipose tissue, called "brown fat."
Appetite regulation
Appetite is regulated by a variety of factors. Orexigenic agents, such as neuropeptide Y (NPY) and Agouti related transcript (AGRT) are agents that increase appetite. Anorexic agents, such as α-melanocyte stimulating hormone (α-MSH) and cocaine and amphetamine related transcript (CART), decrease appetite.
In the short-term, there are a variety of factors that can give you a feeling of "fullness." One of these, stomach stretch, can be played to our advantage by the use of surgery (see here for more details). Other factors include cholecystokinin, glucagon-like peptide, PYY, ghrelin, insulin, and galanin. Except for ghrelin, all of these factors increase after a meal. (Ghrelin secretion is at its maximum when your stomach is empty and decreases as your stomach fills.)
The hypothalamus is fairly important in the satiety response. The ventromedial hypothalamus (VMH), located right next to the third ventricle, is also known as the "satiety centre." When it is stimulated, animals stop eating, but when it is destroyed, animals become hyperphagic (eat a lot). Lateral to the VMH is the lateral hypothalamus (LH), or "feeding centre." When the LH is stimulated, animals eat, but when it is destroyed, fatal anorexia (lack of appetite) occurs. It is thought that the VMH inhibits the LH.
Appetite is regulated by a variety of factors. Orexigenic agents, such as neuropeptide Y (NPY) and Agouti related transcript (AGRT) are agents that increase appetite. Anorexic agents, such as α-melanocyte stimulating hormone (α-MSH) and cocaine and amphetamine related transcript (CART), decrease appetite.
In the short-term, there are a variety of factors that can give you a feeling of "fullness." One of these, stomach stretch, can be played to our advantage by the use of surgery (see here for more details). Other factors include cholecystokinin, glucagon-like peptide, PYY, ghrelin, insulin, and galanin. Except for ghrelin, all of these factors increase after a meal. (Ghrelin secretion is at its maximum when your stomach is empty and decreases as your stomach fills.)
The hypothalamus is fairly important in the satiety response. The ventromedial hypothalamus (VMH), located right next to the third ventricle, is also known as the "satiety centre." When it is stimulated, animals stop eating, but when it is destroyed, animals become hyperphagic (eat a lot). Lateral to the VMH is the lateral hypothalamus (LH), or "feeding centre." When the LH is stimulated, animals eat, but when it is destroyed, fatal anorexia (lack of appetite) occurs. It is thought that the VMH inhibits the LH.
The "lipostat" principle
The "lipostat" principle is the idea that a factor released from fat cells can work to inhibit appetite. This was discovered through parabiosis experiments, in which the capillaries from two mice were grafted together (so that whatever was circulating through the blood in one mouse would circulate through the blood of the other mouse as well). In one experiment, a mouse with a VMH lesion was grafted to a normal mouse. The mouse with the VMH lesion became obese due to the damaged "satiety centre." After some time, the normal mouse became skinny- it lost its appetite due to a circulating factor released by the fat cells in the VMH lesion mouse.
The "lipostat" principle is the idea that a factor released from fat cells can work to inhibit appetite. This was discovered through parabiosis experiments, in which the capillaries from two mice were grafted together (so that whatever was circulating through the blood in one mouse would circulate through the blood of the other mouse as well). In one experiment, a mouse with a VMH lesion was grafted to a normal mouse. The mouse with the VMH lesion became obese due to the damaged "satiety centre." After some time, the normal mouse became skinny- it lost its appetite due to a circulating factor released by the fat cells in the VMH lesion mouse.
Control of leptin secretion
It turns out that the "lipostat" from the parabiosis experiments is leptin. Leptin is a peptide hormone that is secreted by adipose cells, as well as by other cells of the body. Leptin secretion is directly proportional to fat mass, so an increase in body fat increases the secretion of leptin. Leptin suppresses appetite and increases energy expenditure (at least in rodents).
Ob/ob mice are obese and hyperphagic, insulin resistant, and have many other abnormalities. All of these abnormalities were fixed when leptin was administered. This did not, however, happen when leptin was administered to db/db mice, which have a similar phenotype. This is because ob/ob mice were leptin deficient (as the ob gene codes for leptin), whereas db/db mice lacked the leptin receptor and were thus leptin resistant (as the db gene codes for the leptin receptor).
It turns out that the "lipostat" from the parabiosis experiments is leptin. Leptin is a peptide hormone that is secreted by adipose cells, as well as by other cells of the body. Leptin secretion is directly proportional to fat mass, so an increase in body fat increases the secretion of leptin. Leptin suppresses appetite and increases energy expenditure (at least in rodents).
Ob/ob mice are obese and hyperphagic, insulin resistant, and have many other abnormalities. All of these abnormalities were fixed when leptin was administered. This did not, however, happen when leptin was administered to db/db mice, which have a similar phenotype. This is because ob/ob mice were leptin deficient (as the ob gene codes for leptin), whereas db/db mice lacked the leptin receptor and were thus leptin resistant (as the db gene codes for the leptin receptor).
Hypothalamic targets of leptin
The hypothalamus contains leptin receptors (Ob-R). The only leptin receptor that has an intracellular signalling pathway is Ob-Rb, which acts via the JAK/STAT pathway. Leptin downregulates orexigenic agents such as NPY, AGRP, and anandamide, and upregulates anorexic agents such as α-MSH, CART, CRH, urocortin, and GLP-1.
A mechanism for the "munchies"
Apparently smoking marijuana makes you hungry. To explain this, let's take a quick look at anandamide, which I mentioned in the previous paragraph. Anandamide is an orexigenic (appetite-increasing) agent that binds to cannabinoid receptors (CB1 receptors). Cannabis also binds to these receptors, increasing appetite. As such, CB1 antagonists, such as rimonabant, are being tested as possible treatments for obesity.
Apparently smoking marijuana makes you hungry. To explain this, let's take a quick look at anandamide, which I mentioned in the previous paragraph. Anandamide is an orexigenic (appetite-increasing) agent that binds to cannabinoid receptors (CB1 receptors). Cannabis also binds to these receptors, increasing appetite. As such, CB1 antagonists, such as rimonabant, are being tested as possible treatments for obesity.
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