GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Intracerebroventricular injection of ghrelin receptor antagonist alleviated NAFLD via improving hypothalamic insulin resistance.
Gong. Yating Y; Guo. Yaoyao Y; Jiang. Yiming Y; Xing. Zhiyang Z; Zhang. Heng H; Wang. Hongbo H; Gong. Yanling Y
Key Findings
- Central ghrelin receptor blockade reduced serum cholesterol, triglycerides, AST, ALT, and liver fat in NAFLD rats.
- Treatment lowered fasting glucose and insulin, improving HOMA‑IR (a measure of insulin resistance).
- Phosphorylation of the hypothalamic PI3K/Akt/mTOR pathway increased, indicating better insulin signaling in the brain.
Practical Outcomes
- The study suggests that inhibiting ghrelin signaling in the brain could help treat fatty liver disease, but the method (intracerebroventricular injection) isn’t practical for humans. For biohackers, it highlights the importance of ghrelin’s role in metabolism and may prompt interest in peripheral ghrelin antagonists, though more research is needed before any real‑world protocol can be recommended.
Summary
In rats with diet‑induced fatty liver, blocking the brain's ghrelin receptor with a compound called D‑Lys‑3‑GHRP‑6 lowered blood fats, liver enzymes, and insulin resistance, and it reduced fat buildup in the liver. The effect seemed to come from improved insulin signaling in the hypothalamus.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of clinical metabolic syndrome. Insulin resistance is an important factor in the pathogenesis of NAFLD. Ghrelin, widely distributed in peripheral tissues and the central nervous system, plays a vital role in regulating food intake, energy balance, and substance metabolism. In this study, the effect of intracerebroventricular (ICV) injection of ghrelin receptor antagonist on NAFLD was explored. A rat model of NAFLD was established by feeding a high-fat diet, and a selective ghrelin receptor antagonist [D-Lys-3]-GHRP-6 was injected via ventricular intubation implantation. The serum total cholesterol (TC), triglycerides (TGs), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hepatic TGs were measured using the colorimetric method. Fasting plasma glucose (FPG) and fasting plasma insulin (FPI) were determined to calculate homeostatic model assessment insulin resistance (HOMA-IR). Hematoxylin-eosin (HE) and Oil Red O staining were conducted to observe the pathological changes and lipid accumulation in the liver. Hosphatidylinositide3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway protein expressions were measured using western blot analysis. ICV injection of [D-Lys-3]-GHRP-6 significantly reduced serum lipids, transaminase, and HOMA-IR, improved liver injury, and inhibited lipid accumulation in the liver of NAFLD rats. Moreover, ICV injection of [D-Lys-3]-GHRP-6 significantly up-regulated the phosphorylation levels of PI3K/Akt/mTOR signaling protein expressions in the hypothalamus, indicating a significant improvement in hypothalamic insulin resistance. Blockade of central ghrelin receptor can treat NAFLD possibly via the hypothalamic PI3K/Akt/mTOR signaling pathway to improve insulin resistance.
Study Information
pubmed
2022
10.22038/ijbms.2022.64792.14272