Ghrelin

Ghrelin is produced by the stomach. Among its numerous functions, ghrelin increases appetite and stimulates the release of growth hormone.

What is ghrelin?

Ghrelin is a hormone that is produced and released mainly by the stomach with small amounts also released by the small intestine, pancreas and brain.

Ghrelin has numerous functions. It is termed the ‘hunger hormone’ because it stimulates appetite, increases food intake and promotes fat storage. When administered to humans, ghrelin increases food intake by up to 30%; it circulates in the bloodstream and acts at the hypothalamus, an area of the brain crucial in the control of appetite. Ghrelin has also been shown to act on regions of the brain involved in reward processing such as the amygdala, leading to a further enhancement of food intake.

In addition to increasing appetite, ghrelin plays an important role in mediating whole-body glucose and energy homeostasis (i.e. balance). Ghrelin stimulates the release of growth hormone from the pituitary gland, which, unlike ghrelin itself, breaks down fat tissue and causes the build-up of muscle. In the pancreas, ghrelin stimulates the release of glucagon, which increases production and release of glucose from the liver and the fat tissue to the bloodstream. It is also suggested that ghrelin suppresses insulin secretion from the pancreas to reduce glucose storage in key organs.

Ghrelin also has protective effects on the cardiovascular system. In animal models of myocardial infarction, ghrelin promotes vascular network expansion and reduces inflammation, Further studies are needed to enrich our understanding on the physiology of ghrelin in the cardiovascular system.

New studies proposed that ghrelin also plays a key role in mediating memory and stress, which may be the result of unknown signalling pathways of the ghrelin system in the hippocampus and amygdala in the brain. Future work identifying the unknown pathways may lead to development of new drug treatments for neurological diseases such as Parkinson’s disease, anxiety and depression.

How is ghrelin controlled?

Ghrelin levels are primarily regulated by food intake. Levels of ghrelin in the blood rise just before eating and when fasting, with the timing of these rises being affected by our normal meal routine. Hence, ghrelin is thought to play a role in mealtime ‘hunger pangs’ and the need to begin meals. Levels of ghrelin increase when fasting (in line with increased hunger) and are lower in individuals with a higher body weight compared with lean individuals, which suggests ghrelin could be involved in the long-term regulation of body weight.

Eating reduces concentrations of ghrelin. Different nutrients slow down ghrelin release to varying degrees; carbohydrates and proteins restrict the production and release of ghrelin to a greater extent than fats.

Somatostatin also restricts ghrelin release, as well as many other hormones released from the digestive tract.

What happens if I have too much ghrelin?

Ghrelin levels increase after dieting, which may explain why diet-induced weight loss can be difficult to maintain. One would expect higher levels in people with obesity. However, ghrelin levels are usually lower in people with higher body weight compared with lean people, which suggests ghrelin is not a cause of obesity; although there is a suggestion that obese people are actually more sensitive to the hormone. However, more research is needed to confirm this.

Prader-Willi syndrome is a genetic disease in which patients have severe obesity, extreme hunger and learning difficulties. Unlike more common forms of obesity, circulating ghrelin levels are high in Prader-Willi syndrome patients and start before the development of obesity. This suggests that ghrelin may contribute to their increased appetite and body weight.

Ghrelin levels are also high in cachexia and the eating disorder, anorexia nervosa. This may be the body’s way of making up for weight loss by stimulating food intake and fat storage.

Higher levels of ghrelin were also detected in cancer tumours, suggesting ghrelin signalling pathway may promote cancer development.

What happens if I have too little ghrelin?

Gastric bypass surgery, which involves reducing the size of the stomach, is considered to be the most effective treatment for severe, life-threatening obesity. Patients who lose weight after bypass surgery have been found to have lower ghrelin levels than those who lose weight by other means such as diet and exercise, which may partly explain the long-lasting success of this treatment.