Obese Mice Are Protected From Increased Energy Intake in Response to Voluntary Wheel Running

Abstract

Diseases of metabolism pose an increasing threat to public health that has led to greater demand for effective treatments. Obesity is a highly prevalent metabolic disease that afflicts over 100 million Americans and increases the risk of developing diabetes and cardiovascular disease. Lifestyle modifications that incorporate exercise are a standard prescription for obesity, but its effectiveness is limited due to variability in compliance and physiological adaptations (e.g. compensatory increases in energy intake). Previous studies have shown that voluntary exercise fails to induce weight loss in high fat fed mice, but little is known regarding the onset of exercise. Here, we tested the hypothesis that chronic overnutrition from high fat feeding will mitigate the compensatory increase in food intake that commonly accompanies increased energy expenditure from voluntary exercise.Starting at 12 weeks of age, male C57BL/6J mice were weight matched, singly housed and fed a chow (n=8) or high fat diet (HFD; 60% calories from fat; n=6) for 4 weeks. At 18 weeks of age, mice were housed in a Promethion Metabolic Analyzer to measure energy expenditure, food intake and physical activity. Experiments were performed at 21°C with running wheels locked for four days then unlocked for the subsequent nine days. Body composition was assessed both prior to and immediately following indirect calorimetry experiments. Ethoscan (Sable Systems) analysis was performed to examine voluntary wheel running (VWR) distance, duration and speed and measured the time and distance for off‐wheel activities (i.e. roaming and feeding).HF‐fed mice were heavier (WT: 26.9 ± 1.1 vs. HF: 36.8 ± 4.2 g; p < 0.05) and had greater fat mass (WT: 3.5 ± 0.6 vs. HF: 11.1 ± 3.1 g; p < 0.05) than chow‐fed mice prior to energy balance studies. VWR caused a decrease in whole body (WT: −0.3 ± 0.8 vs. HF: −4.0 ± 1.3 g; p > 0.05) and fat mass (WT: 0.3 ± 0.6 vs. HF: −3.0 ± 0.9 g; p < 0.05) in HFD‐fed, but not in chow‐fed mice. VWR distance, duration, and speed were not affected by diet. VWR increased energy expenditure (EE) with both diets equally, but energy intake (EI) only increased in chow‐fed mice. VWR decreased overall off‐wheel activity (OWA) regardless of diet.These data demonstrate that 9 days of VWR cause weight loss in HFD‐fed mice but not mice fed a chow‐diet. Because VWR did not vary between diets, the efficacy of VWR in HFD‐fed mice could instead be attributed to resistance to specific behavioral compensations (i.e. increased food intake) that occur with the introduction of VWR in lean mice.Support or Funding InformationDSL (16POST29910001); D.H.W. (NIH DK054902 and DK076169)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.