Sexual differences in the control of energy homeostasis

Abstract

The prevalence of obesity has reached epidemic proportion with enormous costs in both human lives and healthcare dollars spent. Obesity-related metabolic disorders are much lower in premenopausal women than men; however, there is a dramatic increase following menopause in women. The health risks associated with obesity vary depending on the location of adipose tissue. Adipose tissue distributed in the abdominal visceral carry a much greater risk for metabolic disorders than does adipose tissue distributed subcutaneously. There are distinct sex-dependent differences in the regional fat distribution, women carry more fat subcutaneously whereas men carry more fat viscerally. Males and females differ with respect to their regulation of energy homeostasis. Peripheral adiposity hormones such as leptin and insulin as well as sex hormones directly influence energy balance. Sexual dimorphisms in energy balance, body fat distribution, and the role sex hormones have in mediating these differences are the focus of this review.

Figures

Fig. 1

Potential model depicting how sex hormones and adiposity signals may interact to regulate body fat distribution. We propose that female sex steroid estrogen regulates body fat distribution. Females carry more fat subcutaneously whereas males with lower estrogen carry more fat viscerally. Reductions in estrogen, as occurs in menopause, is associated with an increase in visceral adiposity. Estrogen receptors (ER) are expressed in adipose tissues and hypothalamus. Estrogen regulates energy balance and body fat distribution by either directly interacting with the leptin signaling pathway or through activation of estrogen receptors. Specifically, estrogen may directly act on estrogen receptor alpha (ERα) in visceral adipose tissues to regulate lipid metabolism. Estrogen may influence adiposity by interacting with leptin, and potentially enhancing leptin-induced activation of the sympathetic nervous system which innervates visceral adipose tissue, thereby reducing fat accrual in the visceral depot. Additionally, subcutaneous adipose tissue, which accounts for a higher percentage of adipose tissue in females, secretes leptin, and the secreted leptin may activate CNS leptin receptors, and this may directly influence leptin-induced activation of the sympathetic nervous system.