533-P: A Ketogenic Diet Reduces Blood Glucose and Restores Exercise Training–Induced Improvements in Aerobic Capacity in Hyperglycemic Mice

Abstract

Evidence suggests that hyperglycemia can blunt improvements in aerobic capacity (VO2peak) with exercise training. Accordingly, people with diabetes have lower VO2peak than normoglycemic controls, increasing their risk of complications and mortality. We hypothesized that reducing blood glucose levels with a dietary intervention would restore exercise training-induced improvements in VO2peak in hyperglycemic mice. To test this, we induced hyperglycemia in male CD-1 mice with streptozotocin (STZ) , which increased random blood glucose to 220 ± 31 mg/dL on a standard diet (80% carbohydrate, 10% fat & protein) . A subset of STZ mice was fed a ketogenic (KETO) diet consisting of 90% fat and 10% protein, which reduced blood glucose to 177 ± 26 mg/dL. Eight weeks after starting the dietary intervention, STZ and KETO mice underwent voluntary wheel running or remained sedentary for 8 weeks. Exercise training improved VO2peak and time to exhaustion during a graded exercise test in KETO-fed mice while no significant improvement was observed in STZ mice. Trained STZ and KETO mice had similar fat and lean mass, indicating improved VO2peak in trained KETO mice was independent of body composition. Our data demonstrate that reducing blood glucose using a carbohydrate-restricted diet may restore training-induced improvements in exercise capacity that are prevented by hyperglycemia. Disclosure R.C.Nava: None. E.M.Cooney: None. S.J.Lessard: None. Funding National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) RDK124258 National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) T32 Postdoctoral Training Fellowship 5T32DK007260-45