Rcan2 and estradiol independently regulate body weight in female mice

// Ling-Cui Ding 1 , Qian-Qian Gong 1 , Shi-Wei Li 1 , Xiao-Long Fu 1 , Ye-Cheng Jin 1 , Jian Zhang 1 , Jian-Gang Gao 1 and Xiao-Yang Sun 1 1 Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, China Correspondence to: Xiao-Yang Sun, email: sunxy70@sdu.edu.cn Keywords: Rcan2, 17β-estradiol, ovariectomy, body weight regulation, obesity Received: January 05, 2017     Accepted: May 05, 2017     Published: May 29, 2017 ABSTRACT Rcan2 increases food intake and plays an important role in the development of age- and diet- induced obesity in male mice. However, in females, wild-type mice grow almost at a similar rate as Rcan2 −/− mice on normal chow diet from 6 weeks of age. Here we showed that the ability of Rcan2 to promote weight gain was attenuated by energy expenditure mediated by 17β-estradiol in female mice. Using ovariectomy-operated models, we found that 17β-estradiol deprivation did not alter food intake, but induced more weight gain in wild-type mice than Rcan2 −/− mice. If wild-type mice ingested equally as Rcan2 −/− mice, in the same ovarian state they exhibited similar weight changes, but the mice in ovariectomized groups were significantly heavier than the ovarian-intact mice, suggesting that body weight is not only regulated by Rcan2 , but also by 17β-estradiol. Furthermore, we demonstrated that Rcan2 and 17β-estradiol independently regulated body weight even on high-fat diets. Therefore, our findings indicate that Rcan2 and 17β-estradiol regulate body weight through different mechanisms. Rcan2 increases food intake, whereas 17β-estradiol promotes energy expenditure. These findings provide novel insights into the sexual dimorphism of body weight regulation.