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Leptin&Ghrelin

Leptin&Ghrelin

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Published by Samaah Zohair

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Published by: Samaah Zohair on May 19, 2010
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05/26/2012

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Introduction:
At the beginning of the new century more scientific studies have shown that there reallyexists a hunger hormone in our bodies that transmits the hunger sensation to the brainand urges us to eat large or small amounts of food, depending on everyone's lifestyle.The hunger hormone is called ghrelin and is primarily found in the cells of the stomachepithelial tissue, but also in various areas of the brain and hypothalamus. Before we eatthe levels of ghrelin in our bodies are very high and stimulate brain cells, that "let usknow" that we should eat. After we eat, the levels of the hunger hormone decreaseconsiderably.The counterpart hormone of ghrelin is leptin, released by the adipose tissue. Leptin is the"satiety hormone," as it provides the neuronal cells with satiation signals. When found inelevated levels within our body, the satiety hormone leads to lack of appetite by givingus the impression that we are fed up even if we have not eaten anything since manyhours.Logically, medical experts have linked ghrelin hormone to obesity and eating disorders,and the leptin hormone to lack of appetite disorders such as anorexia or other diseases inwhich patients do not manifest any urge to eat, like when suffering from various types of cancer, AIDS etc. That is why they thought that the treatment for the two types of eating problems - eating too much or too less - should consists of reversing the functions of theappetite hormones. Consequently, ghrelin should be used to enhance hunger in those thatare too skinny and lack the physiological need of eating, while leptin should be used for making obese people eating less.
(1)
Etymology:
--Leptin (Greek leptos meaning thin)The Ob(Lep) gene (Ob for obese, Lep for leptin) is located on chromosome 7 in humans.is a protein hormone that plays a key role in regulating energy intake and energyexpenditure, including appetite and metabolism
(2)
--Ghrelin was named for its ability to provoke growth hormone secretion (the suffix ghremeans "grow")
(3)
Biosynthesis:
Human leptin is a protein of 167 amino acids.It is manufactured primarily in the adipocytes of white adipose tissue ( the major sourceof leptin ) and the level of circulating leptin is directly proportional to the total amountof fat in the body.
 
In addition to white adipose tissue it can also be produced by brown adipose tissue, placenta (syncytiotrophoblasts), ovaries, skeletal muscle, stomach (lower part of fundicglands), mammary epithelial cells, bone marrow, pituitary and liver.Leptin has also been discovered to be synthesized from Gastric Chief Cells and P cells inthe stomach .Leptin receptors are located in the hypothalamus.It is one of the most important adipose derived hormones
(4)ll
Ghrelin is synthesized as a preprohormone, then proteolytically processed to yield a 28-amino acid peptide.The predominant source of circulating ghrelin is the gastrointestinal tract, primarily fromthe stomach, but also in smaller amounts from the intestine. The hypothalamus in the brain is another significant source of ghrelin; smaller amounts are produced in the placenta, kidney, and pituitary gland.Ghrelin receptor was known well before ghrelin was discovered. Cells within theanterior pituitary bear a receptor that, when activated, potently stimulates secretion of growth hormone - that receptor was named the growth hormone secretagogues receptor Ghrelin levels increase before meals and decrease after meals(GHS-R).
(5)
Mechanism of action:
Hunger is the feeling experienced when one has a desire to eat. Satiety is the absence of hunger.The fluctuation of leptin and ghrelin hormone levels results in the motivation of a personto consume food. When he eats, adipocytes trigger the release of leptin into the body.Increasing levels of leptin results in a reduction of one's motivation to eat. After hours of non-consumption, leptin levels drop significantly. These low levels of leptin cause therelease of secondary hormone, ghrelin, which in turn reinitiates the feeling of hunger.Some studies have suggested that an increased production of ghrelin may enhanceappetite evoked by the sight of food, while an increase in stress may also influence thehormone's production. These findings may help to explain why hunger can prevail evenin stressful situations.
(6)
Ghrelin's activity in modulating feeding behavior and energy balance are best explained by the presence of ghrelin receptors in areas of the hypothalamus long known to beinvolved in appetite regulation. Receptors are also found concentrated in other areas of the brain, including the hippocampus and regions which may also be related to thishormone's effects on appetite. Ghrelin-responsiveness of these neurones is both leptin-
 
and insulin-sensitive.
(6)
Function of leptin:
Leptin acts on receptors in the hypothalamus of the brain where it inhibits appetite by:(1) counteracting the effects of neuropeptide Y (a potent feeding stimulant secreted bycells in the gut and in the hypothalamus);2)counteracting the effects of anandamide (another potent feeding stimulant that binds to the same receptors as THC, the active ingredient of marijuana)3) promoting the synthesis of α-MSH, an appetite suppressant(.melanocyte stimulatinghormone).
(7)
 
Roles of leptin:
1) Adiposity signalTo date, only leptin and insulin are known to act as an adiposity signal. In general,Leptin circulates at levels proportional to body fat.It enters the central nervous system (CNS) in proportion to its plasma concentration.Its receptors are found in brain neurons involved in regulating energy intake andexpenditure.It controls food intake and energy expenditure by acting on receptors in the mediobasalhypothalamus
(8)
.2)Leptin & melatonin regulation:There is some controversy regarding the regulation of leptin by melatonin during thenight. One research group suggested that increased levels of melatonin caused a downregulation of leptin. However, in 2004, Brazilian researchers found that in the presenceof insulin, "melatonin interacts with insulin and up-regulates insulin-stimulated leptinexpression", therefore causing a decrease in appetite whilst sleeping.
(9)
3)Interaction with amylin:Co-administration of two neurohormones known to have a role in body weight control,amylin (produced by beta cells in the pancreas) and leptin (produced by fat cells), resultsin sustained, fat-specific weight loss in a leptin-resistant animal model of obesity.
(10)
4)Satiety: appetite control:Leptin binds to neuropeptide Y (NPY) neurons in the arcuate nucleus, in such a way thatdecreases the activity of these neurons. Leptin signals to the brain that the body has had

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