Rong Ping, Mu Yinqiu, Wang Meiqin, Chen Liang, Liu Fangtong, Jin Yuxin, Feng Weikuan, Zhou Kun, Liang Hui, Wang Hong-Yu, Chen Shuai
State Key Laboratory of Pharmaceutical Biotechnology, Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, 210061, China.
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, 210061, China.
Sci China Life Sci. 2025 Jun;68(6):1662-1675. doi: 10.1007/s11427-024-2768-y. Epub 2025 Jan 21.
Insulin-like growth factor 1 (IGF1) is a regulator of both cellular hypertrophy and lipogenesis, which are two key processes for pathogenesis of obesity. However, the in vivo role of IGF1 in the development of obesity remains unclear. Here, we show that IGF1 expression is increased in adipose tissue in obese human patients and animal models. Elevation of IGF1 is associated with increased lipogenic gene expression and decreased energy expenditure. Genetic down-regulation of IGF1 normalizes lipogenic gene expression, restores aberrant energy metabolism and alleviates obese phenotype of a genetic mouse model with IGF1-hypersecretion. Importantly, genetic down-regulation of IGF1 exerts similar effects on development of diet-induced obesity. Furthermore, berberine that is an AMP-activated protein kinase (AMPK) activator in medicinal herbs inhibits IGF1 secretion, decreases lipogenic gene expression and alleviates diet-induced adiposity. Collectively, our findings demonstrate that hypersecretion of IGF1 is a critical factor for the development of obesity and can be targeted using AMPK activators to alleviate obesity.
胰岛素样生长因子1（IGF1）是细胞肥大和脂肪生成的调节因子，而这两个过程是肥胖发病机制的两个关键环节。然而，IGF1在肥胖发生发展中的体内作用仍不清楚。在此，我们表明，在肥胖人类患者和动物模型的脂肪组织中，IGF1表达增加。IGF1升高与脂肪生成基因表达增加和能量消耗减少有关。IGF1的基因下调可使脂肪生成基因表达正常化，恢复异常的能量代谢，并减轻IGF1分泌过多的遗传小鼠模型的肥胖表型。重要的是，IGF1的基因下调对饮食诱导的肥胖发展具有类似作用。此外，作为草药中AMP激活蛋白激酶（AMPK）激活剂的黄连素可抑制IGF1分泌，降低脂肪生成基因表达，并减轻饮食诱导的肥胖。总体而言，我们的研究结果表明，IGF1分泌过多是肥胖发生发展的关键因素，并且可以使用AMPK激活剂作为靶点来减轻肥胖。
