Hypothalamic GHR—SIRT1 Axis in Fasting

Cells

Chidera Ubah¹  Marianna Sadagurski¹  Olesya Didyuk¹  JulianaBezerra Medeiros de Lima¹  LucasKniess Debarba¹  Iven Ayyar¹ 

[1]Department of Biological Sciences, Integrative Biosciences Center (IBio), Wayne State University, Detroit, Michigan, MI 48202, USA

关键词: growth hormone axis;    growth hormone receptor;    Sirtuin 1;    hypothalamus;    arcuate nucleus;   

DOI  :  10.3390/cells10040891

来源: DOAJ

【 摘 要 】

Many aspects of physiological functions are controlled by the hypothalamus, a brain region that connects the neuroendocrine system to whole-body metabolism. Growth hormone (GH) and the GH receptor (GHR) are expressed in hypothalamic regions known to participate in the regulation of feeding and whole-body energy homeostasis. Sirtuin 1 (SIRT1) is the most conserved mamma-lian nicotinamide adenine dinucleotide (NAD⁺)-dependent protein deacetylase that plays a key role in controlling life span and sensing nutrient availability in the hypothalamus in response to caloric restriction. However, the interaction between GHR signaling and SIRT1 in the hypothal-amus is not established. In the arcuate nucleus (ARC) of the hypothalamus, the anorexigenic proopiomelanocortin (POMC)-expressing neurons and the orexigenic agouti-related protein (AgRP)-expressing neurons are the major regulators of feeding and energy expenditure. We show that in the ARC, the majority of GHR-expressing neurons also express SIRT1 and respond to fasting by upregulating SIRT1 expression. Accordingly, hypothalamic upregulation of SIRT1 in response to fasting is blunted in animals with GHR deletion in the AgRP neurons (AgRP^EYFPΔGHR). Our data thus reveal a novel interaction between GH and SIRT1 in responses to fasting.

【 授权许可】

Unknown