463-P: Fuel Expenditure and Deposition in Tissues after Exercise or Low-Fat Diet in Obese Female and Male Mice

Abstract

We hypothesized that a healthy diet and exercise improve energy metabolism through different pathways in males and females. Understanding the mechanism for a how healthy diet vs. exercise improves metabolic outcomes is important for intervention through lifestyle change to target risk factors for obesity-associated diseases in specific populations. Mice were fed a high-fat diet (HFD) for 12 weeks, then divided into 4 groups, followed for 6 weeks: a. HFD; b. HFD + exercise; c. the diet was switched to chow; d. diet-switch + exercise. Instead of acute metabolic effects, we investigated sustained effects of exercise by examining tissue glucose uptake and metabolism 48 hours after the last exercise session. Diet-switch and exercise reduced obesity and fat contents in tissues in both sexes. Muscle glucose uptake was higher in males than females and not different between treatments 48 hours after exercise session. Liver glucose uptake was higher in males than females. Exercise, but not diet-switch, lowered liver glucose uptake, which effect was greater in males than females. Glucose uptake in subcutaneous, visceral, and brown adipose tissues was higher in females than males. Diet-switch, but not exercise, reduced glucose uptake in brown fat, which effect was greater in females than males. Furthermore, Diet-switch decreased the pathways for adipocyte differentiation (PPARγ) and lipogenesis (DGAT1/2) in subcutaneous adipose tissues in females. Muscle protein levels of CPT1β and pACC were increased by diet-switch in both sexes, and by exercise in males only. Our data indicate: 1) adipose tissue nutrient storage is the major energy reservoir that protects against obesity-related metabolic changes in females; 2) with regard to improving metabolic outcomes, diet-switch benefits females more and exercise benefits males more; for both sexes 3) exercise training is more effective in preventing fatty liver than diet-switch, and 4) both diet-switch and exercise promote fat oxidation in muscles. Disclosure J. An: None. L. Zhu: None. S. Yu: None. E. Edington: None. B. Litts: None. J. M. Stafford: None. Funding National Institutes of Health (R01HL144846)