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

Abstract

Obesity is a world-wide problem, and a risk factor for cardiovascular disease, diabetes, cancer and other diseases. It is well established that sex differences influence fat storage. Males and females exhibit differences in anatomical fat distribution, utilization of fat stores, levels of adipose tissue-derived hormones, and obesity co-morbidities. The basis for these sex differences may be parsed into the effects of male vs. female gonadal hormones and the effects of XX vs. XY chromosome complement. Studies employing mouse models that allow the distinction of gonadal from chromosomal effects have revealed that X chromosome dosage influences food intake, which in turn affects adiposity and the occurrence of adverse metabolic conditions such as hyperinsulinemia, hyperlipidemia, and fatty liver. The identification of X chromosome dosage as a player in the behavior and physiology related to obesity suggests novel molecular mechanisms that may underlie sex differences in obesity and metabolism.

A Guide for the Design of Pre-clinical Studies on Sex Differences in Metabolism

“…To identify the contribution of the various components, it is critical to design and analyze experiments with appropriate statistical considerations. A useful paradigm is illustrated by studies performed with the FCG model, where the study of four genotypes (XX and XY mice with male gonads and XX and XY mice with female gonads) lends itself to a 2 × 2 comparison via 2-way ANOVA (Arnold and Chen, 2009; Burgoyne and Arnold, 2016; Chen et al, 2012; Chen et al, 2015; Link et al, 2015; Link et al, 2017; Reue, 2017). If analysis of the four genotypes by ANOVA reveals that mice with male gonads (XX and XY) differ from mice with female gonads (XX and XY), the cause is gonadal sex (or more precisely, the presence vs .…”

Hepatic mitochondrial adaptations to physical activity: impact of sexual dimorphism, PGC1α and BNIP3‐mediated mitophagy

“…As previous evidence suggests that female mice may be protected from diet‐induced metabolic dysfunction in the liver (Hart‐Unger et al . ; Reue, ), we also chose to test if males or females displayed differential hepatic mitochondrial adaptations to physical activity in each genotype. An illustrated representation of the experimental purpose and design is shown in Fig.…”

“…Finally, because females are known to display greater lipid oxidation during exercise (Hedrington & Davis, ) and are known to be protected from steatosis (Hart‐Unger et al . ; Reue, ) we hypothesized that female mice would display greater physical activity‐induced changes in maximal mitochondrial respiratory capacity, ETS protein content and mitophagy compared to male counterparts.…”

“…Using wild-type (WT) mice and mice with targeted deficiencies in liver-specific PGC1α (LPGC1α +/− ) and BNIP3-mediated mitophagy (BNIP3 −/− ) we aimed to determine if intact mitochondrial biogenesis and BNIP3-mediated mitophagy are required for the beneficial mitochondrial adaptations associated with physical activity in the liver. As previous evidence suggests that female mice may be protected from diet-induced metabolic dysfunction in the liver (Hart-Unger et al 2017;Reue, 2017), we also chose to test if males or females displayed differential hepatic mitochondrial adaptations to physical activity in each genotype. An illustrated representation of the experimental purpose and design is shown in Fig.…”

Learning styles and anthropometric indexes of obesity in Mexican adults from primary care / Estilos de aprendizaje e indicadores de obesidad en adultos usuarios del primer nivel de atención en salud

“…Dato que coincide con lo reportado en hombres adultos mexicanos aparentemente sanos (Chacón, Mejía, Paredes y Gómez, 2012). No obstante, Reue, 2017). Por el contrario, el modelo de predicción del peso corporal indica que la CC y el EA reflexivo contribuyen a su incremento.…”