LRG ameliorates steatohepatitis by activating the AMPK/mTOR/SREBP1 signaling pathway in C57BL/6J mice fed a high‑fat diet

Hao,Tao; Chen,Hongying; Wu,Sisi; Tian,Haoming

doi:10.3892/mmr.2019.10304

LRG ameliorates steatohepatitis by activating the AMPK/mTOR/SREBP1 signaling pathway in C57BL/6J mice fed a high‑fat diet

Authors:
- Tao Hao
- Hongying Chen
- Sisi Wu
- Haoming Tian
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Affiliations: Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Core Facility, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: May 28, 2019 https://doi.org/10.3892/mmr.2019.10304
Pages: 701-708

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Abstract

The pathogenesis of nonalcoholic fatty liver disease non‑alcoholic steatohepatitis (NASH) has not been fully elucidated, and there are currently no effective treatments for NASH. The aim of the present study was to explore the therapeutic effects of the glucagon‑like peptide‑1 (GLP‑1) receptor agonist liraglutide (LRG) on NASH and the underlying mechanisms. C57BL6J mice were fed a high‑fat diet (HFD) for 8 weeks to induce hepatic steatosis, and then LRG was injected subcutaneously for 4 weeks. The expression of sterol regulatory element‑binding protein 1 (SREBP1) and adenosine monophosphate‑activated protein kinase (AMPK) as well as the phosphorylation of mechanistic target of rapamycin (mTOR) and p70 ribosomal S6 kinase (p70S6K) were determined by western blot analysis. The intracellular distribution of SREBP1 was assessed by immunofluorescence staining. The results revealed that LRG treatment ameliorated HFD‑induced hepatic lipid accumulation and inhibited body weight gain. In addition, LRG treatment significantly suppressed the expression of hepatic SREBP1 as well as the phosphorylation of mTOR and p70S6K; it also increased the phosphorylation of AMPK and acetyl coenzyme A carboxylase. Furthermore, LRG treatment inhibited the hepatic nuclear translocation of SREBP1. It was suggested that the GLP‑1 receptor agonist LRG may have ameliorated hepatic steatosis by activating the AMPK/mTOR/SREBP1 signaling pathway as opposed to inhibiting body weight gain.

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