Liraglutide Improves Nonalcoholic Fatty Liver Disease in Diabetic Mice by Activating Autophagy Through AMPK/mTOR Signaling Pathway

Zhanlin Liao; Liangzhi Huang; Jun Chen; Ting Chen; Dezhi Kong; Qifeng Wei; Qiao Chen; Bin Deng; Yanyan Li; Shuai Zhong; Zugui Huang

doi:10.2147/DMSO.S447182

Liraglutide Improves Nonalcoholic Fatty Liver Disease in Diabetic Mice by Activating Autophagy Through AMPK/mTOR Signaling Pathway

Diabetes Metab Syndr Obes. 2024 Feb 5:17:575-584. doi: 10.2147/DMSO.S447182. eCollection 2024.

Authors

Zhanlin Liao^#¹, Liangzhi Huang^#¹, Jun Chen², Ting Chen¹, Dezhi Kong¹, Qifeng Wei¹, Qiao Chen¹, Bin Deng¹, Yanyan Li¹, Shuai Zhong¹, Zugui Huang¹

Affiliations

¹ Department of Endocrine, Affiliated Nanping First Hospital of Fujian Medical University, Nanping, Fujian, 353006, People's Republic of China.
² Department of Ophthalmology, Affiliated Nanping First Hospital of Fujian Medical University, Nanping, Fujian, 353006, People's Republic of China.

^# Contributed equally.

Abstract

Background: Type 2 diabetes (T2DM) combined nonalcoholic fatty liver disease (NAFLD) are characterized by metabolic disruptions. Liraglutide has been proved to be effective in T2DM. If LRG could regulate NAFLD combined T2DM has not been reported.

Methods: Intraperitoneal injection of 1% streptozotocin (STZ) plus high-sugar and high-fat diet was used to induce NAFLD combined T2DM animal model. Palmitic acid (200 µmol/L) and glucose (25 mmol/L) incubation were used to induce cell model. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and Western blotting, respectively.

Results: Liraglutide significantly improved the liver injury of NAFLD combined T2DM rats, but Com-C reversed the effect of liraglutide. The decreased AMPK/mTOR signaling pathway in the NAFLD combined T2DM animals was greatly activated by liraglutide. Com-C reversed the protection effects of liraglutide on palmitic acid+glucose induced cell damage.

Conclusion: Liraglutide could greatly alleviate the damage caused by NAFLD+T2DM and palmitic acid+glucose. The protection effects of liraglutide were greatly inhibited by suppressing AMPK/mTOR signaling pathway. This research might provide a novel therapeutic strategy for the prevention and treatment of NAFLD combined T2DM disease.

Keywords: AMPK/mTOR; autophagy; liraglutide; nonalcoholic fatty liver disease; type 2 diabetes.

Grants and funding

This study was funded by Fujian natural science foundation project (2021J011423) and Fujian Provincial Health Commission Science and Technology Plan Project (2021ZD01004).