Targeting IGF1 to alleviate obesity through regulating energy expenditure and fat deposition

Ping Rong; Yinqiu Mu; Meiqin Wang; Liang Chen; Fangtong Liu; Yuxin Jin; Weikuan Feng; Kun Zhou; Hui Liang; Hong-Yu Wang; Shuai Chen

doi:10.1007/s11427-024-2768-y

Targeting IGF1 to alleviate obesity through regulating energy expenditure and fat deposition

Sci China Life Sci. 2025 Jan 21. doi: 10.1007/s11427-024-2768-y. Online ahead of print.

Authors

Ping Rong^{1

2}, Yinqiu Mu^{1

2}, Meiqin Wang^{1

2}, Liang Chen³, Fangtong Liu^{1

2}, Yuxin Jin^{1

2}, Weikuan Feng^{1

2}, Kun Zhou^{1

2}, Hui Liang⁴, Hong-Yu Wang^{5

6}, Shuai Chen^{7

8}

Affiliations

¹ 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.
² MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, 210061, China.
³ College of Life Sciences, Anhui Medical University, Hefei, 230032, China.
⁴ Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, 210029, China.
⁵ 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. [email protected].
⁶ MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, 210061, China. [email protected].
⁷ 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. [email protected].
⁸ MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, 210061, China. [email protected].

PMID: 39843847
DOI: 10.1007/s11427-024-2768-y

Abstract

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.

Keywords: AMPK; IGF1 secretion; TBC1D1; energy metabolism; obesity; phosphorylation.