Metabolic and behavioral responses to high-fat feeding in mice selectively bred for high wheel-running activity

Abstract

Objective: Increased dietary fat intake is a precipitating factor for the development of obesity and associated metabolic disturbances. Physically active individuals generally have a reduced risk of developing these unhealthy states, but the underlying mechanisms are poorly understood. In the present study, we investigated the effects of feeding a high-fat diet (HFD) on obesity development and fuel homeostasis in male and female mice with a trait for increased physical activity and in their controls. Methods: Male and female mice selectively bred for a high level of wheel running behavior over 30 generations and nonselected controls (background strain Hsd:ICR) were maintained on a standard lab chow high-carbohydrate diet (HCD) or on an HFD (60% fat). Food intake, body weight, indirect calorimetry parameters, spontaneous locomotor activity and several hormones relevant to metabolism and energy balance were measured. Results: On HFD, mice reduced food intake and increased body fat mass and plasma leptin levels, with the notable exception of the selected females, which increased their ingested calories without any effects on body mass or plasma leptin levels. In addition, they had an elevated daily energy expenditure (DEE), increased spontaneous cage activity (B700% relative to controls) and higher resting metabolic rate (RMR) on the HFD compared with feeding the HCD. The selected males also had a higher DEE compared with controls, but no interaction with diet was observed. On HCD, adiponectin levels were higher in selected male, but not female, mice relative to controls. A marked increase in the level of plasma adiponectin was observed on the HFD in selected females, an effect of diet that was not observed in selected males. Conclusion: Genetically based high locomotor activity renders female, but not male, mice resistant to HFD-induced obesity by alterations in behavioral, endocrine and metabolic traits that facilitate fat utilization rather than limiting HFD intake. International Journal of Obesity (2008) IntroductionObesity is becoming an increasingly prevalent health problem among individuals in affluent societies, because it is often associated with metabolic derangements such as impaired glucose tolerance, insulin resistance, high blood pressure, dyslipidemia and abdominal obesity. When these metabolic abnormalities are displayed in concert (often referred to as the 'metabolic syndrome'), they have a high risk of developing into life-threatening conditions such as cardiovascular disease and diabetes mellitus type 2 (for review, see Moller and Kaufman 1 ). Consensus exists that increased dietary fat intake in combination with a sedentary lifestyle are precipitating factors (World Health Organization), 2 but the underlying endocrine and metabolic mechanisms are poorly understood.A major part of the current knowledge on the etiology of obesity and the metabolic syndrome has come from studies on rodents subjected to a high-fat diet (HFD). [3][4][5][6][7] In particular, the use of selectively bred and geneticall...

Functional Genomic Architecture of Predisposition to Voluntary Exercise in Mice: Expression QTL in the Brain

“…Wallingford et al (2009) observed that the inhibition of Prcp activity in vivo decreased food intake in wild-type and obese mice, and Prcp-null mice were leaner and shorter than wild-type controls and resistant to high-fat diet-induced obesity (Wallingford et al 2009). Similar phenotypes have been observed in the HR strain of mice utilized here (Swallow et al 1999;Kelly et al 2006;Vaanholt et al 2008).…”

Anti-obesity Effect of <i>Dioscorea oppositifolia</i> Extract in High-Fat Diet-Induced Obese Mice and Its Chemical Characterization

“…Previous researches indicated that feeding a high-fat diet to mice caused a decrease in energy expenditure and an increase in food intake efficiency. 22,23) The mice fed a high-fat diet increased the food intake efficiency up to 1.7-fold of normal diet group in this study. In contrast, the feeding efficiency of obese mice treated with DOB was similar to that of normal diet group.…”

Western diet increases wheel running in mice selectively bred for high voluntary wheel running

“…Other studies have reported no change in home-cage activity levels when on high-fat diet or a high-fat þ high-sucrose diet for male C57Bl/6J and A/J mice. 30 In a study on one HR and one C line (that is, a subset of the lines that we studied), Vaanholt et al 31 found that high-fat diet did not statistically increase home-cage activity in males or females that were housed without wheel access. Bjursell et al 32 used a diet very similar (high fat, high sucrose, 19.6 kJ g À1 ) to that used in this study and observed a decrease in home-cage activity for inbred C57Bl/6J mice.…”

“…53,54 Both mice and human beings seem to exhibit 'compensatory mechanisms' to deal with excess caloric intake, including decreased food intake, increased metabolic rate and increased non-exercise activity thermogenesis 28,31,53,55,56 (but see the review by Westerterp 57 ). The increased wheel running by HR mice on WD (Figure 3) may represent an alternative compensatory mechanism.…”