Journal of Capital Medical University ›› 2019, Vol. 40 ›› Issue (3): 409-416.doi: 10.3969/j.issn.1006-7795.2019.03.016

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Effect of G protein-coupled receptor MAS on hepatic glycolipid metabolism

Zhang Yichen, Cao Xi, Yang Jinkui   

  1. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University;Beijing Key Laboratory of Diabetes Research and Care;Beijing Diabetes Institute, Beijing 100730, China
  • Received:2018-12-06 Online:2019-05-21 Published:2019-06-13
  • Supported by:
    This study was supported by National Natural Science Foundation of China (81670774,81471014,81561128015),Natural Science Foundation of Beijing (7162047).

Abstract: Objective To explore effects of G protein-coupled MAS receptor (MASR) on glycolipid metabolism in human liver. Methods Human hepatocyte cell line HepG2 was infected with MAS adenovirus. Endoplasmic reticulum stress was induced by adding thapsigargin (Tg) to detect triglyceride (TG), total cholesterol (TC) and glycogen content in HepG2 cells. Real-time PCR was used to detect the mRNA levels of endoplasmic reticulum stress-related apoptosis genes and glucose/lipid metabolism related genes in HepG2 cells; Western blotting method was performed for the detection of glucose-6-phosphatase (G6pase), phosphoenol phosphoenolpyruvate carboxykinase (PEPCK), fatty acid synthase (FAS), acetyl-CoA carboxylase α (ACCα), phosphorylated acetyl CoA carboxylase α (p-ACCα); protein level expression.Results Endoplasmic reticulum stress induced the expression of MAS gene, while MAS overexpression significantly decreased the expression of endoplasmic reticulum stress-related genes including C/EBP homologous protein (CHOP), glucose regulated protein (GRP78), activating transcription factor 6 (ATF6), X box-binding protein 1 (Xbp1) and inositol requiring protein 1(IRE1). The expression levels of apoptosis-related genes Bax and Caspase-12 were obviously reduced. MAS overexpression reduced Tg-induced intracellular triglyceride levels, in addition to elevated levels of glycogen in HepG2 cells. At the same time, at the molecular level, the expression of G6pase and PEPCK were down-regulated both in mRNA and protein levels, and the expressions of FAS and ACCα related to lipid synthesis were also down-regulated. Conclusion MAS can improve the glucose and lipid metabolism in HepG2 cells, which may be related to the protective effect of MAS on hepatic endoplasmic reticulum stress and apoptosis.

Key words: MAS receptor, endoplasmic reticulum stress, apoptosis, hepatic glycolipid metabolism

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