Central effects of humanin on hepatic triglyceride secretion

• Published in: American journal of physiology: endocrinology and metabolism 2015-08, Vol.309 (3), p.E283-E292
• Main Authors: Gong, Zhenwei, Su, Kai, Cui, Lingguang, Tas, Emir, Zhang, Ting, Dong, H Henry, Yakar, Shoshana, Muzumdar, Radhika H
• Format: Article
• Language: English
• Subjects: Adiposity - drug effects; Alzheimer's disease; Animals; Anti-Obesity Agents - administration & dosage; Anti-Obesity Agents - pharmacology; Anti-Obesity Agents - therapeutic use; Apoptosis; Carrier Proteins - agonists; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cells, Cultured; Central Nervous System Agents - administration & dosage; Central Nervous System Agents - pharmacology; Central Nervous System Agents - therapeutic use; Diet, High-Fat - adverse effects; Hepatocytes - cytology; Hepatocytes - drug effects; Hepatocytes - metabolism; Homeostasis; Infusions, Intravenous; Infusions, Intraventricular; Intra-Abdominal Fat - drug effects; Intra-Abdominal Fat - pathology; Intracellular Signaling Peptides and Proteins - administration & dosage; Intracellular Signaling Peptides and Proteins - chemistry; Intracellular Signaling Peptides and Proteins - metabolism; Intracellular Signaling Peptides and Proteins - pharmacology; Intracellular Signaling Peptides and Proteins - therapeutic use; Ischemia; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Metabolism; Mice, Inbred C57BL; Models, Biological; Obesity - drug therapy; Obesity - etiology; Obesity - metabolism; Obesity - pathology; Peptides; Peptides - administration & dosage; Peptides - pharmacology; Peptides - therapeutic use; Rats, Sprague-Dawley; Reproducibility of Results; Rodents; Triglycerides - blood; Triglycerides - metabolism; Vagotomy, Truncal
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00043.2015

Humanin (HN) is an endogenous mitochondria-associated peptide that has been shown to protect against various Alzheimer's disease-associated insults, myocardial ischemia-reperfusion injury, and reactive oxygen species-induced cell death. We have shown previously that HN improves whole body glucose homeostasis by improving insulin sensitivity and increasing glucose-stimulated insulin secretion (GSIS) from the β-cells. Here, we report that intraperitoneal treatment with one of HN analogs, HNG, decreases body weight gain, visceral fat, and hepatic triglyceride (TG) accumulation in high-fat diet-fed mice. The decrease in hepatic TG accumulation is due to increased activity of hepatic microsomal triglyceride transfer protein (MTTP) and increased hepatic TG secretion. Both intravenous (iv) and intracerebroventricular (icv) infusion of HNG acutely increase TG secretion from the liver. Vagotomy blocks the effect on both iv and icv HNG on TG secretion, suggesting that the effects of HNG on hepatic TG flux are centrally mediated. Our data suggest that HN is a new player in central regulation of peripheral lipid metabolism.