The sexual dimorphism of obesity

Abstract

The NIH has recently highlighted the importance of sexual dimorphisms and has mandated inclusion of both sexes in clinical trials and basic research. In this review we highlight new and novel ways sex hormones influence body adiposity and the metabolic syndrome. Understanding how and why metabolic processes differ by sex will enable clinicians to target and personalize therapies based on gender. Adipose tissue function and deposition differ by sex. 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 which affords protection from the negative consequences associated with obesity and the metabolic syndrome. 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. Estrogens, directly or through activation of their receptors on adipocytes and in adipose tissues, facilitate adipose tissue deposition and function. Evidence suggests that estrogens augment the sympathetic tone differentially to the adipose tissue depots favoring lipid accumulation in the subcutaneous depot in women and visceral fat deposition in men. At the level of adipocyte function, estrogens and their receptors influence the expandability of fat cells enhancing the expandability in the subcutaneous depot and inhibiting it in the visceral depot. Sex hormones clearly influence adipose tissue function and deposition, determining how to capture and utilize their function in a time of caloric surfeit, requires more information. The key will be harnessing the beneficial effects of sex hormones in such a way as to provide ‘healthy’ adiposity.

Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C

“…These finding suggests that leptin activates TNC via a NOdependent mechanism. Although obesity affects both males and females, a sexual dimorphism exists in the development of obesity-associated metabolic complications 69 . Thus, further studies are warranted to analyze the impact of iNOS disruption in the sexual dimorphism of obesity.…”

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

“…A high fat (HF) diet is believed to cause fat accumulation and consequentially metabolic disorders and is generally used to create valid animal models of obesity and IR [4,5]. The risk of obesity-related comorbidities is well established in men, but less so for age matched pre-menopausal women [6]. There are a number of experimental and clinical studies showing sex differences in the susceptibility to various diseases like IR, T2DM and metabolic syndrome [7][8][9][10][11].…”

Rutumati Lakshanas-Estrus Signaling In Humans

“…Premenopausal women tend to store fat on the hips, thighs and buttocks, giving them a pear shape also called gynoid, or gluteo-femoral pattern of adipose tissue distribution. Women accumulate energy reserves in subcutaneous depot to prepare for adipose tissue mobilization required for lactation [27]. Any feature or marker of stored fat in females, such as larger body, breasts and buttocks is assumed to be attractive to males.…”