Introduction
Ghrelin (/ˈɡrɛlɪn/; or
lenomorelin, INN) is a hormone primarily produced by enteroendocrine cells of
the gastrointestinal tract, especially the stomach, and is also dubbed the
"hunger hormone" because it increases the drive to eat.[6] Blood
levels of ghrelin are highest before meals when hungry, returning to lower
levels after mealtimes. 4Ghrelin may help prepare for food intake by increasing
gastric motility and stimulating the secretion of gastric acid. Ghrelin
activates cells in the anterior pituitary gland and hypothalamic arcuate
nucleus, including neuropeptide Y neurons that initiate appetite. Ghrelin
stimulates brain structures having a specific receptor – the growth hormone
secretagogue receptor 1A (GHSR-1A). Ghrelin also participates in regulation of
reward cognition, learning and memory, the sleep-wake cycle, taste sensation,
reward behavior, and glucose metabolism.
Ghrelin was discovered after the ghrelin receptor (called
growth hormone secretagogue type 1A receptor or GHS-R) was determined in 1999.
The hormone name is based on its role as a growth hormone-releasing peptide- gʰre-, meaning "to
grow".
The ghrelin cell is also known as an A-like cell (pancreas),
X-cell (for unknown function), X/A-like cell (rats), Epsilon cell (pancreas),
P/D sub 1 cell (humans) and Gr cell (abbreviation for ghrelin cell).
Ghrelin cells are found mainly in the stomach and duodenum,
but also in the jejunum, lungs, pancreatic islets, gonads, adrenal cortex,
placenta, and kidney. It has also been shown that ghrelin is produced locally
in the brain. Additionally, research suggests that ghrelin may be produced in
the myocardium and have an 'autocrine/ paracrine' like effect within the heart.
Ghrelin cells are also found in oxyntic glands (20% of cells), pyloric glands,
and small intestine.
Function and mechanism of action
1.
Ghrelin is a participant in
regulating the complex process of energy homeostasis which adjusts both energy
input – by adjusting hunger signals – and energy output – by adjusting the
proportion of energy going to ATP production, fat storage, glycogen storage,
and short-term heat loss. The net result of these processes is reflected in
body weight, and is under continuous monitoring and adjustment based on
metabolic signals and needs. At any given moment in time, it may be in
equilibrium or disequilibrium. Gastric-brain communication is an essential part
of energy homeostasis, and several communication pathways are probable,
including the gastric intracellular mTOR/S6K1 pathway mediating the interaction
among ghrelin, nesfatin and endocannabinoid gastric systems, and both afferent
and efferent vagal signals.
2.
Ghrelin and synthetic
ghrelin mimetics (growth hormone secretagogues) increase body weight and fat
mass by triggering receptors in the arcuate nucleus that include neuropeptide Y
(NPY) and agouti-related protein (AgRP) neurons. Ghrelin responsiveness of
these neurons is both leptin- and insulin-sensitive. Ghrelin reduces the
sensitivity of gastric vagal afferents, so they are less sensitive to gastric
distension.
3.
In addition to its function
in energy homeostasis, ghrelin also activates the cholinergic–dopaminergic
reward link in inputs to the ventral tegmental area and in the mesolimbic
pathway, a circuit that communicates the hedonic and reinforcing aspects of
natural rewards, such as food and addictive drugs such as ethanol. Ghrelin
receptors are located on neurons in this circuit. Hypothalamic ghrelin signaling
is required for reward from alcohol and palatable/rewarding foods.
4.
Ghrelin has been linked
to inducing appetite and feeding behaviors. Circulating ghrelin levels are
the highest right before a meal and the lowest right after. Injections of
ghrelin in humans have been shown to increase food intake in a dose-dependent
manner. So the more ghrelin that is injected the more food that is consumed.
However, ghrelin does not increase meal size, only meal number. Ghrelin also
increases motivation to seek out food.
5.
Body weight is regulated
through energy balance, the amount of energy taken in versus the amount of
energy expended over an extended period of time. Studies have shown that
ghrelin levels are positively correlated with weight. This data suggests that
ghrelin functions as an adiposity signal, a messenger between the body's energy
stores and the brain.
6.
Action on Glucose
metabolism
The entire ghrelin system (dAG, AG, GHS-R and GOAT) has a
gluco-regulatory action,
7.
Effects of and on Sleep
Preliminary research indicates that ghrelin participates in
the regulation of circadian rhythms. A review reported finding strong evidence
that sleep restriction affected ghrelin or leptin levels, or energy
expenditure.
8.
Effects on Cardiovascular
system
Ghrelin functions as a cardio-protective peptide by being an
anti-inflammatory agent, promoting angiogenesis, inhibiting arrhythmia, and
improving heart failure.
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