Genetic Basis for Sex Differences in Obesity and Lipid Metabolism

Abstract

Men and women exhibit significant differences in obesity, cardiovascular disease and diabetes. To provide better diagnosis and treatment for both sexes, it is important to identify factors that underlie the observed sex differences. Traditionally, sex differences have been attributed to the differential effects of male and female gonadal secretions (commonly referred to as “sex hormones”), which do substantially influence many aspects of metabolism and related diseases. Less appreciated as a contributor to sex differences are the fundamental genetic differences between males and females, which are ultimately determined by the presence of an XX or XY sex chromosome complement. Here we review the mechanisms by which gonadal hormones and sex chromosome complement each contribute to lipid metabolism and associated diseases, and the current approaches that are used to study them. We focus particularly on genetic approaches including genome-wide association studies in humans and mice, “–omics” and “systems genetics” approaches, and unique experimental mouse models that allow distinction between gonadal and sex chromosome effects.

Effects of Interval Training on Visceral Adipose Tissue in Centrally Obese 70‐Year‐Old Individuals: A Randomized Controlled Trial

“…In terms of the sex‐specific analyses, there were some interesting, albeit preliminary, findings in the male subcohort, where men in the intervention group decreased both VAT and FM significantly more compared to men in the control group. These findings corroborate those of previous studies on overweight adults, and given that there was no significant difference in adherence between men and women, the hypothesis that there are sex differences in terms of decreasing VAT cannot be ruled out . To that end, it is of interest that we also found sex‐specific effects on functional strength from resistance training in a recent randomized study in a similar cohort as the present .…”

“…These findings corroborate those of previous studies on overweight adults, 17,38,39 and given that there was no significant difference in adherence between men and women, the hypothesis that there are sex differences in terms of decreasing VAT cannot be ruled out. 40 To that end, it is of interest that we also found sex-specific effects on functional strength from resistance training in a recent randomized study in a similar cohort as the present. 32 Even so, it is critical to note that these are merely exploratory findings, requiring further confirmatory research based on larger study samples before any definitive conclusions can be drawn.…”

Body composition in anorexia nervosa: Meta‐analysis and meta‐regression of cross‐sectional and longitudinal studies

“…Overall, the meta‐analyzed study sample was highly selected and biased as it comprised mostly European females aged between 14 and 31 years, emphasizing the urgent need for studies including diverse ancestries, such as Asia, South and Central America, and Africa. Females and males differ in body composition and metabolic characteristics (Karastergiou & Fried, ; Link & Reue, ), underscoring the need for more studies on males with AN. Our study selection was limited by the lack of control groups and underreported extensive sample overlap.…”

Sex differences in obesity: X chromosome dosage as a risk factor for increased food intake, adiposity and co-morbidities

“…Obesity is of medical interest primarily because of its association with co-morbidities such as insulin resistance, hyperlipidemia and fatty liver, which in turn are linked to diseases such as type 2 diabetes mellitus and cardiovascular disease. Sex has been established as a risk factor for these conditions, but the mechanisms explored have consisted almost exclusively of gonadal hormone levels (reviewed in [41]). It was therefore of interest to determine whether XX chromosome complement is a risk factor for co-morbidities of obesity.…”