Liraglutide Improves Non-Alcoholic Fatty Liver Disease In Diabetic Mice By Modulating Inflammatory Signaling Pathways

Abstract

Ying Luo,1,* Pijian Yang,1,* Zhengming Li,2 Yunchen Luo,2 Jing Shen,1 Ruwen Li,1 Hua Zheng,3 Yuzhen Liang,2 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*These authors contributed equally to this workCorrespondence: Yuzhen Liang; Ning Xia Email [email protected]; [email protected]: Many chronic metabolic diseases, such as obesity and type 2 diabetes (T2DM), are closely related to a chronic low-grade inflammatory state in tissues. The high prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with T2DM is related to the role of inflammation in the disease. In this study, we investigated the role of liraglutide in improving lipid metabolism disorders and preventing their progression to NAFLD by modulating inflammatory signaling pathways, thereby providing new treatment options for NAFLD.Methods: We designed a 2×2 factorial analysis experiment. A mouse model of NAFLD with T2DM was established by feeding the animals a high-fat diet (HFD). The NAFLD mice with HFD-induced diabetes were treated with liraglutide for 10 weeks. Hematoxylin and eosin staining, Oil Red O staining and electron microscopy were used to observe the accumulation of triglycerides in the liver. RT-PCR and Western blotting were used to analyze the expression of α-SMA, IL-1β, TNF-α, NF-κB and the NF-κB inhibitory protein IκB in the liver at the gene and protein levels, respectively.Results: Liraglutide reduced the body weight and fasting blood glucose levels of HFD-fed mice. The expression of α-SMA, IL-1β, TNF-α, and NF-κB in the liver of HFD-fed mice was increased at the mRNA and protein levels, but liraglutide treatment decreased the expression of these molecules. The expression of IκB in the liver decreased at the mRNA and protein levels but was upregulated after liraglutide treatment.Conclusion: Based on the current findings, liraglutide can significantly improve hepatic steatosis, primarily by downregulating the expression of inflammatory signaling mediators in the TNF-α pathway.Keywords: liraglutide, nonalcoholic fatty liver disease, inflammatory signaling pathway

Keywords

• liraglutide
• nonalcoholic fatty liver disease
• inflammatory signaling pathway.