Effects of a Ketogenic Diet and Chronic Aerobic Exercise on C57BL6 Mice

Low carbohydrate ketogenic diets (LCKD) alter metabolic processes and have been proposed as a means to attenuate adiposity and reduce hyperglycemia. Aerobic exercise training promotes a suite of metabolic adaptations effective in reducing the incidence of metabolic syndrome. There is potential for combined LCKD and aerobic exercise training to alter substrate metabolism in a manner that could enhance body composition. To investigate whether a LCKD could favorably alter metabolic function and potentiate the effects of chronic aerobic exercise, mice were fed a LCKD for a total of 7 weeks, while during the final 3 weeks half of the mice concurrently engaged in daily treadmill exercise. METHODS 40 C57BL6 mice were randomized into 4 groups (n=10/group): 2 groups were fed a low‐fat control diet (16% protein, 72% carbohydrate, 12% fat) with one group performing vigorous intensity (blood lactate >4mM post‐exercise) daily treadmill exercise (CEX) and the other serving as sedentary controls (CSED). The remaining 2 groups were fed a LCKD (84% fat, 16% protein) with one exercise group (KEX) and a group of sedentary controls (KSED). Body composition (NMR) was measured weekly. At the end of the 4 week exercise training program, mice were euthanized and substrate oxidation was assessed using 14C labelled substrates, while blood was analyzed for lipids, glucose and β‐OHB. RESULTS The LCKD resulted in a mild increase in circulating ketones; however, mice on this diet did not exhibit differences in serum fatty acids, triglycerides (TG), or glucose levels despite consuming a lipid‐enriched, carbohydrate‐deficient diet. Body weight and fat mass increased in response to the LCKD, but exercise training limited weight gain. A LCKD did not alter TG levels in liver or muscle; however, exercise training increased TG accrual in both tissues and this effect was more prominent in mice fed the control diet. In the liver, LCKD reduce carbohydrate oxidation, but increased leucine oxidation, incomplete palmitate oxidation, and peroxisomal oxidation. Alternatively, in skeletal muscle carbohydrate oxidation did not change in response to LCKD, whereas mitochondrial and peroxisomal fat oxidation both increased. Exercise training had minimal effect on hepatic substrate oxidation, but increased oxidation of leucine, palmitate, and lignocerate in skeletal muscle; however, no synergistic effects were detected between a ketogenic diet and exercise training. CONCLUSION Our results indicate that mice fed an 84% fat, 16% protein diet demonstrate a shift in substrate utilization toward an increased reliance on fatty acid and branch‐chain amino acid catabolism in liver and skeletal muscle, while vigorous‐intensity exercise effects were more prominent in muscle. Despite the fact that both LCKD and exercise independently induced shifts in substrate metabolism, the effects do not appear to be additive or synergistic and mice fed an LCKD retained greater adiposity than mice fed a protein‐matched control diet Support or Funding Information This work was supported by NIH R01 DK103860‐01 (R.C.N). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .