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System-wide energy balance requires the coordination of dietary nutrient intake and caloric expenditure. Several hormonal systems in the gut-brain axis monitor tissue metabolic status and trigger neural mechanisms that regulate hunger, satiety, and energy metabolism.

Ghrelin & Obestatin

Ghrelin and Obestatin are proteolytic fragments of the same precursor protein which is primarily expressed in the gastric mucosa. Ghrelin and Obestatin exert multiple actions peripherally and in the brain for the regulation of appetite and energy production.



Leptin is an adipocyte-derived peptide hormone that acts in the hypothalamus to suppress hunger. Leptin resistance is associated with the development of obesity.


Stimulate Appetite

AgRP, ASIP/Agouti, and Orexins are peptide hormones that are expressed in the adrenal and hypothalamus, in adipocytes and pancreas, and in the hypothalamus, respectively. Among their other functions, AgRP and Orexins stimulate appetite, while ASIP enhances insulin production.

Melanocortin is a peptide hormone secreted by hypothalamic neurons. It counteracts AgRP action by functioning as an appetite suppressant and stimulator of glucose uptake.



Cholecystokinin (CCK) is a peptide hormone that is released by intestinal enteroendocrine cells and acts through receptors in the brain, pancreas, and stomach. It plays a role in insulin secretion, gallbladder contraction, and appetite suppression.