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phase 2Weight Loss & Diabetes

Ghrelin

Also known as: GHRL, Lenomorelin, Growth Hormone Release-Inducing Peptide, Appetite-Regulating Hormone

Ghrelin is a 28-amino-acid peptide hormone predominantly produced by oxyntic cells of the gastric fundus, functioning as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a). It is the only known circulating orexigenic (appetite-stimulating) hormone, earning its designation as the "hunger hormone." Ghrelin levels rise preprandially and fall postprandially, orchestrating meal initiation, energy homeostasis, growth hormone release, and gastric motility.

3 cited references·5 researched benefits

Quick Answer

Ghrelin is a 28-amino-acid "hunger hormone" produced primarily in the stomach. As the only known circulating appetite-stimulating hormone, it rises before meals and falls after eating. It activates GHS-R1a receptors to stimulate growth hormone release, increase appetite, promote gastric motility, and regulate energy balance. Research into ghrelin-targeted therapies focuses on obesity, cachexia, gastroparesis, and growth hormone deficiency.

Key Facts

Mechanism
Ghrelin is synthesized as preproghrelin in gastric X/A-like cells and undergoes unique octanoylation at Ser-3 by ghrelin O-acyltransferase (GOAT), producing acyl-ghrelin — the only form that activates GHS-R1a. Receptor activation couples to Gq/11 signaling, increasing intracellular calcium and stimulating GH release from anterior pituitary somatotrophs. In the hypothalamic arcuate nucleus, ghrelin activates NPY/AgRP neurons (orexigenic) and inhibits POMC/CART neurons (anorexigenic), powerfully driving appetite. Vagal afferent signaling from the stomach to the nucleus tractus solitarius provides an additional pathway for meal initiation. Des-acyl ghrelin (the unacylated form, ~90% of circulating ghrelin) does not activate GHS-R1a but may have independent metabolic effects through unidentified receptors.
Research Status
phase 2
Half-Life
~30 minutes
Molecular Formula
C₁₄₉H₂₄₉N₄₇O₄₂
Primary Use
Weight Loss & Diabetes
Table of Contents

Benefits

  • Growth hormone stimulation — potent GH secretagogue through direct pituitary GHS-R1a activation, producing GH pulses comparable to GHRHstrong
  • Appetite stimulation — the only known circulating orexigenic hormone; IV ghrelin increases food intake by 28% in healthy volunteersstrong
  • Cachexia treatment potential — ghrelin and ghrelin mimetics (anamorelin) improve lean body mass and appetite in cancer-associated cachexiamoderate
  • Gastroparesis improvement — accelerates gastric emptying through vagal and enteric nervous system pathwaysmoderate
  • Cardioprotective effects — preclinical data showing improved cardiac output and reduced cardiac remodeling post-myocardial infarctionpreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intravenous infusion (research)1–5 mcg/kgSingle dose or short-term infusionUsed in clinical research settings for GH stimulation tests and appetite studies. Not commercially available as a therapeutic product. Acyl-ghrelin must be used (des-acyl ghrelin is inactive at GHS-R1a).
Subcutaneous injection (research)3–5 mcg/kg1–3× daily in cachexia trialsInvestigational use in cachexia and gastroparesis studies. Short half-life limits efficacy; synthetic mimetics (anamorelin, MK-677) are preferred for sustained GHS-R1a activation.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Increased appetite and food intake — the primary pharmacological effect, which can be undesirable in non-cachectic populationscommon
  • Transient hyperglycemia — ghrelin suppresses insulin secretion and increases hepatic glucose outputcommon
  • Flushing and warmth — vasodilatory effects observed during IV administrationcommon
  • GI discomfort — stomach rumbling (borborygmi) and mild abdominal discomfort at higher dosescommon
  • Potential tumor growth promotion — ghrelin receptors are expressed on some tumors; long-term safety in cancer patients requires further studyserious

Frequently Asked Questions

Why is ghrelin called the "hunger hormone"?
Ghrelin is the only known hormone that circulates in the bloodstream and stimulates appetite. Its levels rise sharply before meals (peaking 1–2 hours before habitual meal times) and fall rapidly after eating. When administered intravenously to healthy volunteers, ghrelin increases food intake by approximately 28% and enhances the subjective sensation of hunger. No other circulating hormone has this orexigenic effect — all other gut hormones (PYY, GLP-1, CCK) are satiety signals that suppress appetite.
What is the difference between acyl-ghrelin and des-acyl ghrelin?
Acyl-ghrelin has an octanoyl (8-carbon fatty acid) group attached to Ser-3 by the enzyme GOAT, and this acylation is required for GHS-R1a receptor binding and biological activity (appetite stimulation, GH release). Des-acyl ghrelin lacks this modification and comprises ~90% of circulating ghrelin. While des-acyl ghrelin cannot activate GHS-R1a, emerging evidence suggests it may have independent effects on glucose metabolism and cell proliferation through unidentified receptors. Some researchers propose des-acyl ghrelin as a counterregulatory signal to acyl-ghrelin.
Why are ghrelin levels high in anorexia nervosa but low in obesity?
Ghrelin acts as an energy-deficit signal. In anorexia nervosa, chronic caloric restriction drives ghrelin to very high levels as the body attempts to stimulate food intake — but patients with anorexia appear to have resistance to ghrelin's orexigenic effects. In obesity, ghrelin levels are chronically suppressed, likely due to persistent caloric excess. After weight loss (including bariatric surgery), ghrelin levels rise, which is one mechanism driving weight regain. Roux-en-Y gastric bypass, which removes most ghrelin-producing gastric tissue, uniquely suppresses this post-weight-loss ghrelin surge.
How does ghrelin relate to GH secretagogue peptides like GHRP-6 and ipamorelin?
Ghrelin is the endogenous ligand for the GHS-R1a receptor, the same receptor targeted by synthetic growth hormone secretagogues (GHS) including GHRP-6, GHRP-2, hexarelin, and ipamorelin. These synthetic peptides were actually developed before ghrelin's discovery in 1999 — ghrelin was identified as the natural hormone that activates the "orphan" GHS receptor. MK-677 (ibutamoren) is a non-peptide oral GHS-R1a agonist. All these compounds stimulate GH release through the same receptor but differ in selectivity, potency, and off-target effects (particularly on appetite, cortisol, and prolactin).

References

  1. 1
    Ghrelin is a growth-hormone-releasing acylated peptide from stomach(1999)PubMed ↗
  2. 2
    Ghrelin, a novel growth hormone-releasing peptide, in the regulation of energy balance and growth hormone secretion(2001)PubMed ↗
  3. 3
    Ghrelin and the regulation of energy balance — a review(2007)PubMed ↗

Latest Research

Last updated: 2026-02-19