Original Article
Effect of liraglutide on hepatic lipid metabolism in high-fat induced obese mice
Huang Yujie, Guo Wancheng, Ju Mengxian, Wang Junjun, Yi Shuxin, Fang Penghua, Zhang Zhenwen
Published 2022-07-20
Cite as Chin J Diabetes Mellitus, 2022, 14(7): 704-710. DOI: 10.3760/cma.j.cn115791-20220106-00010
Abstract
ObjectiveTo investigate of the mechanism of liraglutide regulation of high-fat-induced hepatic lipid metabolism in mice.
MethodsEighteen healthy male C57BL/6 mice were randomly divided into three groups: normal control group (NC group), obesity control group (OC group) and liraglutide group (six mice in each group). Mice in NC group were fed with low-fat diet, and mice in OC group and liraglutide group were fed with high-fat diet for 12 weeks to establish the high-fat induced obesity mouse model. Then, liraglutide group was intraperitoneally injected with 400 μg·kg-1·d-1 for 7 days, equal volumes of saline were injected intraperitoneally into the NC and OC groups. Adipose tissue and liver weight were measured. Body weight, fasting blood glucose, glucose tolerance and insulin resistance, serum and liver triglyceride (TG) and total cholesterol (TC) levels were measured. Serum insulin, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) levels were measured by enzyme-linked immunosorbent assay. The mRNA levels of silent information regulator 1 (SIRT-1), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and phosphoenolpyruvate carboxykinase (PEPCK) in liver were detected by polymerase chain reaction. The protein expression levels of mouse liver SIRT-1, PGC-1α and PEPCK, were detected by Western blotting. One-way analysis of variance (ANOVA) was used for comparison between groups.
ResultsCompared with NC group, in OC group, body weight, fat weight, fasting blood glucose and fasting insulin levels were increased (P<0.05), glucose and insulin tolerance levels were decreased (P<0.05), serum TG, TC, IL-6 and TNF-α levels and liver TG, liver TC and liver weight were increased (P<0.05), however, liver SIRT-1, PGC-1α, PEPCK mRNA and protein levels were decreased (P<0.05). Compared with the OC group, in the liraglutide group, body weight, fat weight, fasting blood glucose and fasting insulin levels were decreased (P<0.05), glucose and insulin tolerance levels were increased (P<0.05), serum insulin, IL-6, TNF-α and triglycerides were significantly decreased (P<0.05), liver lipids were reduced (P<0.05), however, liver SIRT-1, PGC-1α, PEPCK mRNA and protein levels were significantly increased (P<0.05).
ConclusionsLiraglutide improved glucolipid metabolism, increased hepatic fatty acid oxidation and reduced hepatic fat accumulation in high-fat diet-induced obese mice, and the mechanism might be related to activation of hepatic SIRT-1/PGC-1α/PEPCK pathway.
Key words:
Diabetes; Obesity; Liraglutide; Liver; Lipid metabolism
Contributor Information
Huang Yujie
Department of Endocrinology, Clinical Medical College of Yangzhou University, Yangzhou 225001, China
Guo Wancheng
Department of Endocrinology, Clinical Medical College of Yangzhou University, Yangzhou 225001, China
Ju Mengxian
Department of Endocrinology, Clinical Medical College of Yangzhou University, Yangzhou 225001, China
Wang Junjun
Department of Endocrinology, Clinical Medical College of Yangzhou University, Yangzhou 225001, China
Yi Shuxin
Department of Endocrinology, Clinical Medical College of Yangzhou University, Yangzhou 225001, China
Fang Penghua
Experimental Research Center of Clinical Medicine, First Medical School of Nanjing University of Chinese Medicine, Nanjing 210023, China
Zhang Zhenwen
Department of Endocrinology, Clinical Medical College of Yangzhou University, Yangzhou 225001, China
