title: Central effects of humanin on hepatic triglyceride secretion.
abstract: 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.
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
authors.forename: Kai
authors.initials: K
authors.lastname: Su
authors.affiliation: Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York; and.
authors.forename: Lingguang
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
authors.forename: Emir
authors.initials: E
authors.lastname: Tas
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
authors.forename: H Henry
authors.initials: HH
authors.lastname: Dong
authors.affiliation: David B. Kriser Dental Center, Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York.
authors.forename: Shoshana
authors.initials: S
authors.lastname: Yakar
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; radhika.muzumdar@chp.edu.
authors.forename: Radhika H
authors.initials: RH
authors.lastname: Muzumdar
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002352:Carrier Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D059305:Diet, High-Fat / Q000009:adverse effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007262:Infusions, Intravenous; D057967:Infusions, Intraventricular; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009765:Obesity / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*; D015167:Vagotomy, Truncal
chemical_list: D019440:Anti-Obesity Agents; D002352:Carrier Proteins; D002491:Central Nervous System Agents; C000602199:HNG peptide; D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D014280:Triglycerides; C427211:humanin; C106092:microsomal triglyceride transfer protein
keywords: hepatic microsomal triglyceride transfer protein; humanin; hypothalamus; triglyceride secretion