What Is Ghrelin?
Ghrelin, or the hunger hormone, is produced primarily by the stomach.
This hormone is released as a signal to the brain that the stomach is empty and it is time to eat.
Levels of ghrelin increase between mealtimes and reduce when the stomach is full.
While obese individuals have low ghrelin levels, people who restrict their caloric intake are found to have higher levels of the hormone.
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Besides telling your brain you are hungry, ghrelin performs several other functions, such as:
- Increases your food intake
- Helps your body store fat
- Triggers your pituitary gland to release the growth hormone
- Controls sugars in the body and regulates your body’s insulin release
- Protects muscles from weakness
- Participates in bone formation and metabolism
Due to its multifunctional nature, ghrelin is a multifaceted gut hormone.
How Does Ghrelin Regulate Hunger?
When empty, the stomach releases ghrelin that travels through the blood to reach the brain.
Here, it acts on the hypothalamus (part of the brain that produces hormones to regulate multiple body functions, including hunger and thirst).
In the hypothalamus, ghrelin activates the growth hormone secretagogue receptor that stimulates hunger.
Ghrelin also activates gastric acid production, which ensures digestion after a meal.
Other parts of the digestive system, like the small intestine and pancreas, also produce small amounts of ghrelin.
Studies have shown that people who are trying to lose weight or have recently lost weight have higher ghrelin levels.
This increases their hunger levels, making it difficult to maintain weight loss.
Image: Hunger regulation by leptin and ghrelin hormones
Ghrelin and Type 2 Diabetes
Studies have reported that ghrelin plays a role in glucose balance in the body and may cause type 2 diabetes.
A study conducted in 2003 stated that low ghrelin is independently associated with type 2 diabetes, insulin resistance, and elevated blood pressure.
So, ghrelin may have a role to play in the development of type 2 diabetes.
A mutation (genetic change) associated with low ghrelin plasma concentration is the Arg51GIn.
Ghrelin concentrations are low in people with metabolic conditions like type 2 diabetes.
Many studies report that ghrelin inhibits insulin secretion, causing elevated blood glucose levels or type 2 diabetes.
Ghrelin and Obesity
Ghrelin levels are lower in overweight individuals than in lean individuals.
In fact, ghrelin levels are high in people with anorexia nervosa or cachexia.
This shows how the body makes up for weight loss by inducing food intake and fat storage.
Increased appetite may lead to weight gain, and ghrelin regulates hunger and appetite.
Ghrelin also tells the body to decrease the burning of brown fat (Brown fat burning increases overall calorie burning, enabling weight loss).
Besides appetite, ghrelin also influences your sleep-wake cycle, taste sensation, and reward-seeking behavior.
While ghrelin does not directly contribute to obesity, its levels increase after dieting.
This makes it difficult to lose weight or sustain diet-induced weight loss.
Further studies are required to understand the correlation between ghrelin and obesity.
The Ghrelin Receptor Gene – GHSR
Growth Hormone Secretagogue Receptor or GHSR is a member of the G-protein coupled receptor family.
It is located on the q arm of chromosome 3.
This gene gives instructions for producing a protein that participates in homeostasis and regulates body weight.
How Does The Ghrelin Receptor Gene Work?
Ghrelin hormone binds to the GHSR receptor and activates the downstream signaling pathways like cAMP response element (CRE) mediated transportation.
Along with its several molecules, this pathway brings about appetite regulation, energy homeostasis, fat accumulation, mood regulation, cognitive functions, and reward-related food behavior.
Role Of Ghrelin Receptor Gene Variants In Type 2 Diabetes and Obesity
So far, no study has identified a clear relationship between GHSR gene variants and obesity or type 2 diabetes.
However, a few findings from a 2008 study that may be worth noting are:
- Individuals with the GG genotype of single nucleotide polymorphism (SNP) rs490683 lost less weight during a lifestyle intervention than those with the CC genotype.
- People with the AA genotype of SNP 9819506 showed a lower body weight.
None of the polymorphisms in the GHSR gene have so far been associated with type 2 diabetes.
Summary: Ghrelin Receptor Gene
- The stomach produces ghrelin, or the hunger hormone, when empty.
- Besides regulating hunger, ghrelin helps store body fat, controls sugar levels, protects muscles from weakness, and regulates metabolism.
- Ghrelin activates the growth hormone secretagogue receptor in the hypothalamus to stimulate hunger and increase food intake.
- People who restrict their dietary intake or have lost weight tend to have high ghrelin levels.
- Some polymorphisms of the GHSR gene are being studied for their association with obesity and type 2 diabetes.
- So far, no conclusive studies indicate a clear relationship between ghrelin and obesity and type 2 diabetes.
References
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584420/
- https://www.genecards.org/cgi-bin/carddisp.pl?gene=GHSR
- https://eje.bioscientifica.com/view/journals/eje/161/2/307.xml
- https://my.clevelandclinic.org/health/body/22804-ghrelin
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049314/
- https://www.medicalnewstoday.com/articles/ghrelin-all-about-the-hunger-hormone#What-causes-ghrelin-levels-to-rise?
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756630/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2491902/
