Ghrelin
Definition
A 28-amino-acid peptide hormone produced primarily by the stomach that stimulates appetite. Often called the 'hunger hormone'. Rises before meals and falls after eating; chronically suppressed after sleeve gastrectomy.
Ghrelin
Ghrelin is a 28-amino-acid peptide hormone produced primarily by P/D1 cells in the gastric fundus, with smaller contributions from the proximal small intestine, pancreas, and several other tissues. It is the only known orexigenic (appetite-stimulating) gut peptide. Circulating ghrelin rises before meals, peaks just before eating, and falls after food intake, with the magnitude of the post-meal drop correlated with caloric intake and macronutrient composition.
Ghrelin acts via the growth hormone secretagogue receptor (GHSR-1a), expressed prominently in the hypothalamic arcuate nucleus, where it activates neuropeptide Y / agouti-related peptide neurons that drive feeding. It also stimulates growth hormone secretion (hence the original name), modulates gastric motility, and has effects on reward and motivation circuits, contributing to hedonic eating.
In obesity research, ghrelin matters most for two reasons. First, sleeve gastrectomy bariatric surgery removes the gastric fundus and chronically lowers ghrelin levels by approximately 50-70%, contributing to the durable appetite suppression observed after that procedure. Second, weight loss by diet alone typically increases ghrelin (a compensatory response that drives the well-known difficulty of maintaining diet-induced weight loss), and one open question with GLP-1-class pharmacotherapy is the long-term effect on ghrelin and on the post-treatment ghrelin rebound that may contribute to weight regain after discontinuation.
Retatrutide does not directly target ghrelin, but its powerful appetite suppression mediated by GLP-1, GIP, and central pathways appears to override the orexigenic drive of ghrelin signaling during treatment. The effect on ghrelin after retatrutide discontinuation has not yet been characterized.