title: Fat adaptation followed by carbohydrate restoration increases AMPK activity in skeletal muscle from trained humans.
abstract: 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 O2 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-alpha1 and -alpha2 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 Ser221), 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-alpha1 activity after HCHO (P = 0.03) but not Fat-adapt. Exercise was associated with an increase in pACC at Ser221 for both dietary treatments (P < 0.05), with postexercise pACC Ser221 higher after Fat-adapt (P = 0.02). In conclusion, compared with HCHO, Fat-adapt increased resting muscle triglyceride stores and resting AMPK-alpha1 and -alpha2 activity. Fat-adapt also resulted in higher rates of whole body fat oxidation, reduced muscle glycogenolysis, and attenuated the exercise-induced rise in AMPK-alpha1 and AMPK-alpha2 activity compared with HCHO. Our results demonstrate that AMPK-alpha1 and AMPK-alpha2 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.
authors.affiliation: Exercise Metabolism Group, School of Medical Sciences, RMIT University, Victoria, Australia.
authors.forename: Wee Kian
authors.initials: WK
authors.lastname: Yeo
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lessard
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Chen
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Garnham
authors.forename: Louise M
authors.initials: LM
authors.lastname: Burke
authors.forename: Donato A
authors.initials: DA
authors.lastname: Rivas
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Kemp
authors.forename: John A
authors.initials: JA
authors.lastname: Hawley
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000222:Adaptation, Physiological; D000328:Adult; D018592:Cross-Over Studies; D050528:Diet, Carbohydrate-Restricted; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D004734:Energy Metabolism; D015444:Exercise; D006003:Glycogen / Q000378:metabolism*; D050261:Glycogenolysis; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D012119:Respiration; D015398:Signal Transduction; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D014280:Triglycerides; D006003:Glycogen; C526181:PRKAA2 protein, human; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; D000103:Acetyl-CoA Carboxylase