GH-releasing peptide-2 increases fat mass in mice lacking NPY: indication for a crucial mediating role of hypothalamic agouti-related protein.
Tschöp. Matthias M; Statnick. Michael A MA; Suter. Todd M TM; Heiman. Mark L ML
Key Findings
- Daily peripheral GHRP‑2 injections raise food intake and body weight in both normal and NPY‑deficient mice.
- Weight gain is due to increased fat mass (and bone mass) without added lean muscle.
- GHRP‑2 raises hypothalamic AGRP expression, and blocking AGRP with a melanocortin agonist stops the weight gain in NPY‑deficient mice.
Practical Outcomes
- For biohackers, GHRP‑2 could be considered a tool to promote weight and fat gain, potentially useful for overcoming severe under‑eating or cachexia‑like states. However, the evidence is limited to mice, so human dosing, safety, and effectiveness remain uncertain. Until human data emerge, use should be cautious and likely restricted to research settings rather than everyday self‑optimization.
Summary
In mice, the ghrelin‑like peptide GHRP‑2 makes you eat more and store extra fat even when a key appetite hormone (NPY) is missing. The weight gain seems to be driven partly by another brain protein called AGRP. This shows that ghrelin‑receptor drugs can push the body into a positive energy balance and could be useful for conditions where people lose weight, but the study is in rodents, not humans.
Abstract
Ghrelin, an endogenous GH secretagogue, is capable of stimulating adiposity in rodents. Because such adiposity was thought to be mediated by hypothalamic NPY neurons, we investigated by which mechanism a synthetic ghrelin receptor agonist, GHRP-2, would generate a positive energy balance in NPY-deficient [Npy(-/-) mice] and wild-type controls. A dose-dependent increase in body weight and food intake was observed during daily sc injections with GHRP-2. Pre- and posttreatment analysis of body composition indicated increased fat mass and bone mass but not lean mass. Respiratory quotient was increased in GHRP-2-treated mice, indicating preservation of fat. Hypothalamic mRNA levels of agouti- related protein (AGRP), an orexigenic melanocortin receptor antagonist, increased after GHRP-2 treatment. Competitive blockade of AGRP action by melanocortin-receptor agonist MT-II prevented GHRP-induced weight gain in Npy(-/-) mice. In conclusion, chronic peripheral treatment with a ghrelin receptor agonist induced a positive energy balance leading to fat gain in the absence of NPY. These effects could be mediated in part by AGRP. To date, there are few therapeutics that can produce a positive energy balance. Ghrelin receptor agonists offer a treatment option for syndromes like anorexia nervosa, cancer cachexia, or AIDS wasting.
Study Information
pubmed
2002
2002-02-01T00:00:00.000Z
10.1210/endo.143.2.8633
99
60