Short-term GLP-1 receptor agonist exenatide ameliorates intramyocellular lipid deposition without weight loss in ob/ob mice
Short-term GLP-1 receptor agonist exenatide ameliorates intramyocellular lipid deposition without weight loss in ob/ob mice
复制标题
短期 GLP-1 受体激动剂艾塞那肽改善 ob/ob 小鼠肌细胞内脂质沉积而不减轻体重
DOI：
10.1038/s41366-019-0513-y
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发表时间：
2020-01
影响因子：
4.9
通讯作者：
Fen Xu;H. Cao;Zonglan Chen;Huimin Gu;Wanrong Guo;B. Lin;J. Weng
中科院分区：
文献类型：
--
作者：
Fen Xu;H. Cao;Zonglan Chen;Huimin Gu;Wanrong Guo;B. Lin;J. Weng
ObjectiveEctopic lipid deposition is closely associated with type 2 diabetes (T2D). Accumulating evidence shows that GLP-1 receptor agonists (GLP-1 RAs) improve obesity and liver steatosis. However, it remains unknown whether and how they ameliorate lipid deposition in skeletal muscle. This study aimed to investigate the effect of exenatide (a GLP-1 RA) on intramyocellular lipid deposition in the skeletal muscle of T2D models and its dependence on weight loss.MethodsOb/ob mice and diet-induced obese (DIO) mice were treated with exenatide (24 nmol/kg), leptin (1 mg/kg), or saline control intraperitoneally once daily for 4 weeks. Phenotypic evaluations were performed during and after the intervention. PA-induced myoblast C2C12 cells were used as an in vitro model. The expression of key enzymes involved in lipid metabolism was assessed in the skeletal muscle of ob/ob mice and DIO mice.ResultsIn ob/ob mice, 4-week exenatide treatment did not improve the body weight and fat mass, but modestly ameliorated intramyocellular lipid deposition and lipid profiles. In DIO mice, it remarkably alleviated the body weight, lipid profiles, and intramyocellular lipid deposition. In the skeletal muscle of these two models, exenatide treatment activated the AMP-activated protein kinase (AMPK) signaling pathway, stimulated lipid oxidation enzymes, and upregulated the insulin signaling pathway. In vitro, exendin-4 activated the AMPK signaling pathway and stimulated lipid metabolism to improve lipid accumulation in palmitate-induced myoblast C2C12 cells.ConclusionsExenatide ameliorated intramyocellular lipid deposition without body weight reduction in ob/ob mice, but alleviated body weight and intramyocellular lipid deposition in DIO mice. The underlying mechanism included the activation of AMPK signaling pathway and improvement in insulin sensitivity, independent of weight loss in ob/ob mice.
