Central effects of humanin on hepatic triglyceride secretion

Zhenwei Gong, Kai Su, Lingguang Cui, Emir Tas, Ting Zhang, H. Henry Dong, Shoshana Yakar, Radhika H. Muzumdar

Research output: Contribution to journalArticle

Abstract

Humanin (HN) is an endogenous mitochondria-associated peptide that has been shown to protect against various Alzheimer’s diseaseassociated 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. humanin; triglyceride secretion; hepatic microsomal triglyceride transfer protein; hypothalamus.

Original languageEnglish (US)
Pages (from-to)E283-E292
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume309
Issue number3
DOIs
StatePublished - Aug 5 2015

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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