Sex differences in diurnal rhythms of food intake in mice caused by gonadal hormones and complement of sex chromosomes

Abstract

We measured diurnal rhythms of food intake, as well as body weight and composition, while varying three major classes of sex-biasing factors: activational and organizational effects of gonadal hormones, and sex chromosome complement (SCC). Four Core Genotypes (FCG) mice, comprising XX and XY gonadal males and XX and XY gonadal females, were either gonad-intact or gonadectomized (GDX) as adults (2.5 months); food intake was measured second-by-second for 7 days starting 5 weeks later, and body weight and composition were measured for 22 weeks thereafter. Gonadal males weighed more than females. GDX increased body weight/fat of gonadal females, but increased body fat and reduced body weight of males. After GDX, XX mice had greater body weight and more fat than XY mice. In gonad-intact mice, males had greater total food intake and more meals than females during the dark phase, but females had more food intake and meals and larger meals than males during the light phase. GDX reduced overall food intake irrespective of gonad type or SCC, and eliminated differences in feeding between groups with different gonads. Diurnal phase of feeding was influenced by all three sex-biasing variables. Gonad-intact females had earlier onset and acrophase (peak) of feeding relative to males. GDX caused a phase-advance of feeding, especially in XX mice, leading to an earlier onset of feeding in GDX XX vs. XY mice, but earlier acrophase in GDX males relative to females. Gonadal hormones and SCC interact in the control of diurnal rhythms of food intake.

Homeostatic effects of exercise and sleep on metabolic processes in mice with an overexpressed skeletal muscle clock

“…The unmasking of different metabolic profiles with sex is not a surprise. In recent years, several studies have used the sex chromosome complement model to unmask differences in rhythms of activity [22], food intake [22, 23], and lipoprotein levels [24]. …”

Genetic Basis for Sex Differences in Obesity and Lipid Metabolism

“…The weight difference between XX and XY mice was amplified by a high fat diet, becoming statistically significant after merely 3 days on the diet. The increased obesity in XX mice was associated with increased food intake during the light (inactive) phase of the circadian cycle (21, 22). Along with increased adiposity, XX mice developed fatty liver and had elevated levels of fasting insulin (Figure 5), both of which are co-morbidities of obesity in humans.…”

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

“…The major effect of chromosome complement on energy balance was on food intake. Continual monitoring of FCG mouse food intake for several days [24] to weeks [25] revealed that 4 weeks after gonadectomy, female mice tend to eat more than male mice during the dark phase, but that during the light phase XX mice eat more than XY mice, regardless of the original gonad type. The difference between female and male food intake at 4 weeks post- gonadectomy may be attributable to lingering effects of gonadal hormones, as this effect was not apparent at 10 months after gonadectomy [24].…”

“…The difference between female and male food intake at 4 weeks post- gonadectomy may be attributable to lingering effects of gonadal hormones, as this effect was not apparent at 10 months after gonadectomy [24]. Interestingly, the increased food intake in XX compared to XY mice was associated with a shift in feeding rhythm, with early onset of feeding at the end of the light phase in anticipation of normal feeding time at the beginning of the dark phase [25]. There is evidence that altered circadian cycle or increased feeding during the light phase of the circadian cycle leads to increased weight gain in mice [26–28].…”