Wang Mengjie, Pugh Seamus M, Daboul Judy, Miller David, Xu Yong, Hill Jennifer W
Center for Diabetes and Endocrine Research, University of Toledo College of Medicine, Toledo, Ohio, USA.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
bioRxiv. 2024 Jul 4:2024.07.02.601722. doi: 10.1101/2024.07.02.601722.
Kisspeptin, encoded by the gene, ties puberty and fertility to energy status; however, the metabolic factors that control -expressing cells need to be clarified.
To evaluate the impact of IGF-1 on the metabolic and reproductive functions of kisspeptin producing cells, we created mice with IGF-1 receptor deletion driven by the promoter (IGF1R mice). Previous studies have shown IGF-1 and insulin can bind to each other's receptor, permitting IGF-1 signaling in the absence of IGF1R. Therefore, we also generated mice with simultaneous deletion of the IGF1R and insulin receptor (IR) in -expressing cells (IGF1R/IR mice).
Loss of IGF1R in cells caused stunted body length. In addition, female IGF1R mice displayed lower body weight and food intake plus higher energy expenditure and physical activity. This phenotype was linked to higher proopiomelanocortin (POMC) expression and heightened brown adipose tissue (BAT) thermogenesis. Male IGF1R mice had mild changes in metabolic functions. Moreover, IGF1R mice of both sexes experienced delayed puberty. Notably, male IGF1R mice had impaired adulthood fertility accompanied by lower gonadotropin and testosterone levels. Thus, IGF1R in -expressing cells impacts metabolism and reproduction in a sex-specific manner. IGF1R/IR mice had higher fat mass and glucose intolerance, suggesting IGF1R and IR in -expressing cells together regulate body composition and glucose homeostasis.
Overall, our study shows that IGF1R and IR in have cooperative roles in body length, metabolism, and reproduction.
由该基因编码的亲吻素将青春期和生育能力与能量状态联系起来；然而，控制表达该基因的细胞的代谢因子仍需阐明。
为了评估胰岛素样生长因子-1（IGF-1）对产生亲吻素的细胞的代谢和生殖功能的影响，我们创建了由该启动子驱动的IGF-1受体缺失的小鼠（IGF1R小鼠）。先前的研究表明IGF-1和胰岛素可以相互结合对方的受体，从而在缺乏IGF1R的情况下实现IGF-1信号传导。因此，我们还生成了在表达该基因的细胞中同时缺失IGF1R和胰岛素受体（IR）的小鼠（IGF1R/IR小鼠）。
该细胞中IGF1R的缺失导致体长发育迟缓。此外，雌性IGF1R小鼠体重和食物摄入量较低，能量消耗和身体活动较高。这种表型与促阿片黑素皮质素（POMC）表达增加和棕色脂肪组织（BAT）产热增加有关。雄性IGF1R小鼠的代谢功能有轻微变化。此外，两性的IGF1R小鼠青春期均延迟。值得注意的是，雄性IGF1R小鼠成年后的生育能力受损，伴有促性腺激素和睾酮水平降低。因此，表达该基因的细胞中的IGF1R以性别特异性方式影响代谢和生殖。IGF1R/IR小鼠有更高的脂肪量和葡萄糖不耐受性，表明表达该基因的细胞中的IGF1R和IR共同调节身体组成和葡萄糖稳态。
总体而言，我们的研究表明，该基因中的IGF1R和IR在体长、代谢和生殖方面具有协同作用。
