Fat adaptation followed by carbohydrate restoration increases AMPK activity in skeletal muscle from trained humans

Yeo WK, Lessard SJ, Chen ZP, Garnham AP, Burke LM, Rivas DA, Kemp BE, Hawley JA. Fat adaptation followed by carbohydrate restoration increases AMPK activity in skeletal muscle from trained humans. J Appl Physiol 105: 1519-1526, 2008. First published September 18, 2008; doi:10.1152/japplphysiol.90540.2008.-We have previously reported that 5 days of a high-fat diet followed by 1 day of high-carbohydrate intake (Fat-adapt) increased rates of fat oxidation and decreased rates of muscle glycogenolysis during submaximal cycling compared with consumption of an isoenergetic high-carbohydrate diet (HCHO) for 6 days (Burke et al. J Appl Physiol 89: 2413-2421, 2000; Stellingwerff et al. Am J Physiol Endocrinol Metab 290: E380-E388, 2006). To determine potential mechanisms underlying shifts in substrate selection, eight trained subjects performed Fat-adapt and HCHO. On day 7, subjects performed 1-h cycling at 70% peak O-2 uptake. Muscle biopsies were taken immediately before and after exercise. Resting muscle glycogen content was similar between treatments, but muscle triglyceride levels were higher after Fat-adapt (P < 0.05). Resting AMPK-alpha(1) and-alpha(2) activity was higher after Fat-adapt (P = 0.02 and P = 0.05, respectively), while the phosphorylation of AMPK's downstream target, acetyl-CoA carboxylase (pACC at Ser(221)), tended to be elevated after Fat-adapt (P = 0.09). Both the respiratory exchange ratio (P < 0.01) and muscle glycogen utilization (P < 0.05) were lower during exercise after Fat-adapt. Exercise increased AMPK-alpha(1) activity after HCHO (P = 0.03) but not Fat-adapt. Exercise was associated with an increase in pACC at Ser(221) for both dietary treatments (P < 0.05), with postexercise pACC Ser(221) higher after Fat-adapt (P = 0.02). In conclusion, compared with HCHO, Fat-adapt increased resting muscle triglyceride stores and resting AMPK-alpha(1) and-alpha(2) activity. Fat-adapt also resulted in higher rates of whole body fat oxidation, reduced muscle glycogenolysis, and attenuated the exercise-induced rise in AMPK-alpha(1) and AMPK-alpha(2) activity compared with HCHO. Our results demonstrate that AMPK-alpha(1) and AMPK-alpha(2) activity and fuel selection in skeletal muscle in response to exercise can be manipulated by diet and/or the interactive effects of diet and exercise training.