Divergent Energy Expenditure Impacts Mouse Metabolic Adaptation to Acute High-Fat/High-Sucrose Diet Producing Sexually Dimorphic Weight Gain Patterns

Abstract

ABSTRACTObjectiveLong-term weight gain can result from cumulative small weight increases due to short-term excess caloric intake during weekends and holidays. Increased physical activity may mediate weight gain through increases in energy expenditure (EE) and reductions in energy balance. Current methods for modulating mouse EE (e.g. – exercise, chemical uncouplers, etc.) have confounding effects. However, it is known that mouse EE linearly increases as housing temperature decreases below the thermoneutral zone.MethodsTo determine how robust differences in baseline EE impact 7-day changes in weight and body composition on low-fat and high-fat, high-sucrose (HFHS) diets, we performed indirect calorimetry measurements in male and female mice housed at divergent temperatures (20°C vs. 30°C).ResultsAs expected, mice housed at 30°C have ∼40% lower total EE and energy intake compared to 20°C mice regardless of diet or sex. Energy balance was increased with HFHS in all groups, with ∼30% greater increases observed in 30°C versus 20°C mice. HFHS increased weight gain regardless of temperature or sex. Interestingly, no HFHS-induced weight gain differences were observed between females at different temperatures. In contrast, 30°C male mice on HFHS gained ∼50% more weight than 20°C males, and ∼80% more weight compared to 30°C females. HFHS increased fat mass across all groups but 2-fold higher gains occurred in 30°C mice compared to 20°C mice. Females gained ∼35% less fat mass than males at both temperatures.ConclusionsTogether, these data reveal an interaction between divergent ambient temperature-induced EE and sex that impacted diet-induced patterns of short-term weight gain and body composition.HighlightsUtilized ambient temperature differences as an experimental tool to study the impact of divergent baseline energy expenditure on metabolic adaptation to high-fat, high-sucrose diet.Baseline energy expenditure and sex interact to impact diet-induced changes in body composition and weight gain.The energy expenditure and sex interaction is a result of an inverse relationship between fat mass gain and weight-adjusted total energy expenditure, as well as, diet-induced non-shivering thermogenesis.These data support that the hypothesis that higher energy expenditure amplifies the coupling of energy intake to energy expenditure during energy dense feeding, resulting in reduced positive energy balance and reduced gains in weight and adiposity.First evidence that energy expenditure level plays a role in the composition of weight gained by female mice during acute HFHS feeding.This study further highlights issues with obesity/energy metabolism research performed in mice at sub-thermoneutral housing temperatures, particularly with sex comparisons.GRAPHIC ABSTRACTLegend: Male and female mice housed at 30°C had lower energy expenditure (EE) & energy intake (EI), while having greater energy balance (EB), during 7-day high-fat/high-sucrose (HFHS) feeding compared to male and female mice, respectively, housed at 20°C. However, female mice had lower EB compared to males at both housing temperature. Female mice housed at 30°C gained less weight than 30°C males but gained the same relative amount of fat mass during acute HFHS feeding. Interestingly, 20°C females gained the same amount of weight as 20°C males but gained primarily fat-free mass, while the males gained the same proportion of fat as 30°C males and females.