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The role of estrogen in determining sexual dimorphism in energy balance.

Energy balance is determined by caloric intake and the rate at which energy is expended, with the latter comprised of resting energy expenditure, physical activity and adaptive thermogenesis. The regulation of both energy intake and expenditure exhibit clear sexual dimorphism, with young women being relatively protected against weight gain and the development of cardiometabolic diseases. Preclinical studies have indicated that females are more sensitive to the satiety effects of leptin and insulin compared to males. Furthermore, females have greater thermogenic activity than males, whereas resting energy expenditure is generally higher in males than females. In addition to this, in post-menopausal women, the decline in sex steroid concentration, particularly in estrogen, is associated with a shift in the distribution of adipose tissue and overall increased propensity to gain weight. Estrogens are known to regulate energy balance and weight homeostasis via effects on both food intake and energy expenditure. Indeed, 17β-estradiol treatment increases melanocortin signalling in the hypothalamus to cause satiety. Furthermore, estrogenic action at the ventromedial hypothalamus has been linked with increased energy expenditure in female mice. We propose that estrogen action on energy balance is multi-faceted and is fundamental to determining sexual dimorphism in weight control. Futhermore, evidence suggests that the decline in estrogen levels leads to increased risk of weight gain and development of cardiometabolic disease in women across the menopausal transition. Abstract figure legend A schematic illustration highlighting the key role of estrogen in the protection against weight gain and cardiometabolic disease in young reproductive age women. High concentrations of estrogens in young women are associate with differences in adipose tissue distribution, such that adipose is primarily accumulated in the gynoid subcutaneous regions compared to the android adipose phenotype typically seen in men and post-menopausal women. In addition, circulating levels of estrogen in women of reproductive age are associated with inherent changes in energy expenditure including increased physical activity and adaptive thermogenesis. These differences in body composition and energy balance are thought to underpin relative resistance to weight gain and improved metabolic health in young women. This article is protected by copyright. All rights reserved.