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

• Published in: Drug design, development and therapy development and therapy, 2019-12, Vol.13, p.4065-4074
• Main Authors: Luo, Ying, Yang, Pijian, Li, Zhengming, Luo, Yunchen, Shen, Jing, Li, Ruwen, Zheng, Hua, Liang, Yuzhen, Xia, Ning
• Format: Article
• Language: English
• Subjects: Analysis; Animal experimentation; Animals; Antidiabetics; Blood glucose; Body weight; Cytokines; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - chemically induced; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diet; Diet, High-Fat - adverse effects; Disease; Disease Models, Animal; Electron microscopy; Factorial analysis; Fasting; Fatty liver; FDA approval; Food; Gene expression; Genes; Glucose; High fat diet; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacology; IL-1β; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; inflammatory signaling pathway; Insulin resistance; Laboratory animals; Lipid metabolism; Lipids; Liraglutide; Liraglutide - administration & dosage; Liraglutide - pharmacology; Liver; Liver diseases; Male; Medical research; Messenger RNA; Metabolic disorders; Metabolic syndrome; Mice; Mice, Inbred C57BL; Microscopy; mRNA; NF-κB protein; Non-alcoholic Fatty Liver Disease - chemically induced; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - metabolism; nonalcoholic fatty liver disease; Obesity; Oils & fats; Original Research; Peptides; Pharmacology; Physiological aspects; Polymerase chain reaction; Prevention; Proteins; RNA; Signal transduction; Signal Transduction - drug effects; Signaling; Staining; Steatosis; Triglycerides; Tumor necrosis factor-α; Type 2 diabetes; Variance analysis; Weight control; Western blotting
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S224688

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. 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. 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. 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.