Ghrelin
Definition
A 28-amino-acid hormone made mainly by the stomach that drives appetite, the 'hunger hormone'. It rises before meals, falls after eating and stays low after sleeve gastrectomy.
Ghrelin
Ghrelin is a 28-amino-acid peptide hormone made mainly by P/D1 cells in the gastric fundus (the upper part of the stomach), with smaller amounts from the upper small intestine, pancreas and several other tissues. It is the only known gut hormone that stimulates appetite. Blood ghrelin rises before meals, peaks just before eating and falls after you eat. How far it falls depends on how many calories you ate and what kind of food it was.
Ghrelin acts through the growth hormone secretagogue receptor (GHSR-1a), found especially in the hypothalamic arcuate nucleus. There it switches on neuropeptide Y / agouti-related peptide neurons that drive eating. It also stimulates growth hormone release (hence its original name), affects stomach motility and acts on reward and motivation circuits, which feeds pleasure-driven eating.
In obesity research, ghrelin matters for two main reasons. First, sleeve gastrectomy removes the gastric fundus and permanently lowers ghrelin by about 50-70%, which helps explain the lasting appetite suppression after that operation. Second, weight loss from dieting alone usually raises ghrelin. This compensating response is part of why diet-driven weight loss is so hard to keep off. An open question for GLP-1-class drugs is their long-term effect on ghrelin, and whether a ghrelin rebound after stopping treatment contributes to weight regain.
Retatrutide does not target ghrelin directly, but its strong appetite suppression through GLP-1, GIP and brain pathways appears to override ghrelin’s hunger signal during treatment. What happens to ghrelin after retatrutide is stopped has not yet been studied.