Functional Study Of Rcan2 Gene On Body Weight Regulatory Mechanisms In Females

Obesity has become a global health problem over the past several decades,and greatly increased the risk for diabetes and other diseases.So many researchers focus their studies on the regulatory mechanisms of body weight and the reasons for obesity.The regulations of body weight are thought to be sexually dimorphic.Men and postmenopausal women have greater risk of developing obesity and the associated co-morbidities,while premenopausal women tend to remain a lean body shape.Previous studies showed that estrogen can increase metabolic activity and inhibit feeding behavior in females.However,recent researches suggest that the levels of estrogen do not affect food intake,but have effect on energy expenditure.Estrogen is mainly secreted by the ovary.Ovariectomy and hormone replacement experiments demonstrated that the lower estrogen level is the major reason for weight changes in ovariectomized mice.Recently,we reported that Rcan2 gene can increase food intake and promotes weight gain by using an Rcan2 knock-out mouse model.Further analyzing the phenotype of the mice,we found that in male mice,wild-type mice continued to gain more weight by ingesting more food.While on normal chow diet(NCD),the growth curves of wild-type female mice were nearly parallel to those of Rcan2-/-mice,a phenomenon contradicting to our hypothesis that Rcan2 promotes weight gain due to increasing food intake.Since in females estrogen plays a crucial role in the regulation of body weight,it is supposed that the function of Rcan2 gene may be affected by that of estrogen.Therefore,we analyze the phenotypes of Rcan2 knock-out mice under the condition of estrogen deprivation by using the ovariectomy surgery.The results of the study showed that ovariectomy did not change the expression of the Rcan2 gene,but significantly increased the weight differences between wild mice and Rcan2 knockout mice.The food intake measurements revealed that Rcan2 regulates food intake independent of estrogen level.Pair-feeding experiments showed that although ovarectomy significantly increased body weight and adipose mass in mice,at the same estrogen state,if wild-type mice ingested same amount of food with Rcan2-/-mice,the similar weight changesuggesting that body weight is not only regulated by estrogen level,but also Rcan2 gene.In summary,our results suggest that Rcan2 gene and estrogen may regulate body weight through different mechanisms in female,Rcan2 gene increases food intake and promotes weight gain,while estrogen increases energy metabolism,and there are interactions between them on a NCD feeding.We will further determine the mechanisms that Rcan2 gene regulates food intake and estrogen mediates the energy metabolism.This study will enhance our understanding of body weight regulation and explain the gender differences at the development of obesity.It will also provide new therapeutic thoughts and strategies for obesity in postmenopausal women.