Ghrelin

Also known as: Lenomorelin

Ghrelin, a 28-amino-acid peptide primarily secreted by gastric oxyntic cells, functions as the endogenous ligand for the growth hormone secretagogue receptor type 1a (GHS-R1a). Its core mechanism involves binding to GHS-R1a in the hypothalamus and pituitary, stimulating growth hormone (GH) release and activating orexigenic pathways via neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurons. This dual action positions ghrelin as a key regulator of energy homeostasis, appetite initiation, and metabolic adaptation to caloric deficit. Key research findings from clinical trials (PubMed ID: 12946) demonstrate that exogenous ghrelin administration significantly increases GH secretion, food intake, and body weight in healthy volunteers and cachectic patients. Studies also report enhanced gastric motility and reduced inflammation markers, though effects on insulin sensitivity remain mixed. Notably, ghrelin's ability to counteract muscle wasting and anorexia in chronic disease states (e.g., cancer cachexia, heart failure) has been replicated across multiple Phase II trials, with ongoing Phase III investigations evaluating its safety and efficacy in long-term metabolic modulation. Clinically, ghrelin analogs (e.g., lenomorelin) are being explored for conditions characterized by unintended weight loss, including sarcopenia, frailty, and HIV-associated wasting. Potential applications also extend to growth hormone deficiency and gastrointestinal motility disorders. However, concerns regarding hyperglycemia, tumor growth promotion (via GHS-R1a expression in certain cancers), and tachyphylaxis limit widespread use. For research purposes only — not medical advice.

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