ReviewThe sexual dimorphism of obesity
Introduction
Over the past 20 years, adult and childhood obesity rates have doubled, while adolescent obesity has tripled (Ford et al., 2014). Two-thirds of Americans are currently at-risk for obesity related mortality or morbidity however this differs by sex. While the connection between obesity and risk of heart disease, hypertension, cancer, stroke, and diabetes is well established in men, it is less so for women and the mechanisms underlying these sexually dimorphic influences remain poorly understood. Over the past decade adipose tissues have been determined to be more than a storage vessel for triglycerides, rather, these tissues actively contribute to metabolic homeostasis by secreting a wide variety of signaling molecules and hormones. An often underappreciated finding is that adipose tissue function and deposition differ by sex. Females have an overall higher total body fat content when compared to men. Importantly, females differ with respect to distribution of adipose tissues, males tend to accrue more visceral fat, leading to the classic android body shape which has been highly correlated to increased cardiovascular risk; whereas females accrue more fat in the subcutaneous depot prior to menopause, a feature associated with protection from the negative consequences associated with obesity and the metabolic syndrome (Fig. 1). After menopause, fat deposition and accrual shift to favor the visceral depot. This shift is accompanied by a parallel increase in metabolic risk reminiscent to that seen in men. A full understanding of the physiology behind why, and by what mechanisms, adipose tissues accumulate in specific depots and how these depots differ metabolically by sex is important in efforts of prevention of obesity and chronic disease. A review of sex differences in obesity/adipose tissue distribution is timely given that obesity has recently been classified as a disease, and that the National Institutes of Health has made it mandatory to explore gender differences in disease states.
Section snippets
Estrogens and adiposity
Obesity is influenced by a number of variables such as ethnicity, socioeconomic status and education which makes it difficult in humans to determine whether a biological difference per se exists regarding the propensity to gain weight between men and women. By contrast, in animal models where non-biological factors are excluded, studies suggest the propensity toward development of obesity differs between the sexes and this is directly due to sex hormones. For example, female rats gain less
Sexual dimorphism and fat distribution
Premenopausal women tend to store fat on the hips, thighs and buttocks, giving them a pear shape also called gynoid, or gluteal–femoral pattern of adipose tissue distribution. Men accumulate fat predominately in the abdominal region giving them an apple shape also referred to as android, or abdominal pattern of fat accrual (Fig. 1). Even lean men carry a greater proportion of their body fat in the visceral depot as compared to lean women.
Differences in adipose tissue distribution are tied to
Visceral vs subcutaneous adipose tissue and metabolic function
Visceral fat is a source of proinflammatory cytokines that contribute to insulin resistance. In addition, the high lipolytic rate of visceral fat generates large amounts of free fatty acids that are delivered to the liver causing increased hepatic glucose production, hyperinsulinemia, and other features of the metabolic syndrome (Shulman, 2014). By contrast, accumulation of fat in the subcutaneous depot is an independent predictor of lower cardiovascular and diabetes-related mortality, and
Visceral and subcutaneous adipocytes differ
Accumulating evidence suggests obesity complications result from the inability of fat cells to expand and safely store lipids (Fig. 2), which leads to ectopic deposition of lipids in other tissues termed lipotoxicity which results in insulin resistance (Shulman, 2014). Expansion of fat mass can occur either by an increase in volume of preexisting adipocytes (hypertrophy) or by hyperplasia in which an increase in fat mass occurs through recruitment of new preadipocytes. When fat cells surpass
Estrogens and ‘browning’ of adipose tissues
Estrogens not only influence adipose tissue hyperplasia/hypertrophy and distribution, but they also influence the metabolic activity of adipose tissues by regulating ‘browning’, or enhancing the metabolic activity of adipose tissues (Fig. 3). Brown adipose tissue is metabolically more active due to the increased number of mitochondria. Recent data suggest the metabolic rate per kilogram adipose tissue is higher in women than men due to higher levels of brown adipose tissue in women and
Teleological explanation for sex differences in adipose tissue deposition
The evolutionary basis as to why women preferentially store fat in the gluteal–femoral region is not known; however, one hypothesis is that women accumulate energy reserves in the subcutaneous depot to prepare for adipose tissue mobilization required for lactation. Longitudinal studies of skin-fold thickness during pregnancy and lactation consistently show fat accumulation in the supra-iliac and mid-thigh regions (subcutaneous adipose tissue depots) during pregnancy, which is mobilized
Summary
In this review we have demonstrated that estrogens, directly or through activation of their receptors on adipocytes and in adipose tissues, facilitate adipose tissue deposition and function. Estrogens not only are protective in women, but a recent report by Finkelstein et al. further demonstrates that estrogens are necessary in men. Blocking conversion of androgens to estrogens resulted in reductions in insulin sensitivity and decrements in metabolism (Finkelstein et al., 2013). Evidence
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