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Liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2/PI3K/Akt signaling pathway

Authors Yang P, Liang Y, Luo Y, Li Z, Wen Y, Shen J, Li R, Zheng H, Gu HF, Xia N

Received 26 February 2019

Accepted for publication 16 April 2019

Published 4 July 2019 Volume 2019:12 Pages 1013—1021

DOI https://doi.org/10.2147/DMSO.S206867

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Justinn Cochran

Peer reviewer comments 2

Editor who approved publication: Dr Juei-Tang Cheng


Pijian Yang1,*, Yuzhen Liang2,*, Yunchen Luo,2 Zhengming Li,2 Yumei Wen,1 Jing Shen,1 Ruwen Li,1 Hua Zheng,3 Harvest F Gu4,*, Ning Xia1,*

1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China; 3Life Sciences Institute, Guangxi Medical University, Nanning 530021, People’s Republic of China; 4Center for Pathophysiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009 People’s Republic of China

*These authors contributed equally to this work

Purpose: High prevalence of nonalcoholic fatty liver disease (NAFLD) among patients with type 2 diabetes has implicated the role of hepatic insulin resistance (IR) in the diseases. To better understand the underlying mechanism, we have evaluated the pathophysiological effects of Liraglutide on NAFLD via the insulin signaling pathway.
Patients and methods: A 2×2 factorial experiment was designed. High-fat diet (HFD)-induced NAFLD mice with diabetes were treated with Liraglutide for 10 weeks, while the control mice were saline-treated. Hepatic expressions of InsR, IGF-1R, IRS2, PI3K and Akt at mRNA and protein levels were analyzed with RT-PCR and Western blotting. Hematoxylin and eosin staining, Oil Red O staining and electron microscopy were used to visualize triglyceride accumulation in liver.
Results: Liraglutide significantly decreased body weight, fasting blood glucose levels and HOMA-IR scores in HFD mice. Compared with the control mice fed with chow diet, hepatic expressions of InsR, IRS2, PI3K and Akt at both mRNA and protein levels in HFD mice were significantly reduced, but upregulated after Liraglutide treatment. Furthermore, Liraglutide treatment was found to improve hepatic steatosis.
Conclusion: The current study thereby provides evidence that Liraglutide ameliorates NAFLD and improves hepatic steatosis mainly by upregulation of the IRS2/PI3K/Akt signaling mediators.

Keywords: glucagon like peptide 1, Liraglutide, nonalcoholic fatty liver disease, insulin resistance, insulin signaling

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