A novel anti-obesity mechanism for liraglutide by improving adipose tissue leptin resistance in high-fat diet-fed obese mice

Endocrine journal

article

Xiaorui Lyu¹  Kemin Yan¹  Xin Wang¹  Hanyuan Xu¹  Xiaonan Guo¹  Huijuan Zhu¹  Hui Pan¹  Linjie Wang¹  Hongbo Yang¹  Fengying Gong¹ 

[1] Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College

关键词: Liraglutide;    Anti-obesity;    Leptin resistance;    Signal transducer and activator of transcription 3 (STAT3);    Antioxidant enzymes;   

DOI  :  10.1507/endocrj.EJ21-0802

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

Liraglutide has been approved for the treatment of obesity in the past few years. Both oxidative stress and leptin resistance are the critical drivers of obesity. The present study investigated the mechanism of liraglutide protection against obesity by ameliorating leptin resistance and oxidative stress. Male C57BL/6J mice were fed a high-fat diet (HFD) and subcutaneously injected with 200 μg/kg/d liraglutide for 20 weeks. Body weight, fat mass, serum levels of leptin, insulin, and superoxide dismutase (SOD) activities were measured. In addition, glucose and insulin tolerance tests were performed. The expressions of leptin, its signaling genes, and antioxidant enzymes were detected using RT-qPCR and western blot methods in liver and white adipose tissue (WAT) of mice. The results depicted that liraglutide treatment significantly slowed weight gain of body, reduced the fat mass, ameliorated glucose and lipid metabolism, and hepatic steatosis in HFD-fed obese mice. Further study demonstrated that liraglutide treatment resulted in decreased serum levels and the transcript levels of leptin as well as leptin signaling inhibitory regulators. However, it increased leptin receptor expression and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) in WAT (p < 0.05). In addition, the antioxidant enzyme expression was elevated in both liver and WAT of liraglutide-treated mice (p < 0.05). In conclusion, liraglutide conspicuously prevented obesity and ameliorated glucose and lipid metabolism in obese mice through a novel mechanism that improves peripheral leptin resistance in WAT and enhance the antioxidant enzyme expression in both liver and WAT.

【 授权许可】

Unknown