title: AMPK-α2 is involved in exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following high-fat diet.
abstract: AMP-activated protein kinase (AMPK) has been studied extensively and postulated to be a target for the treatment and/or prevention of metabolic disorders such as insulin resistance. Exercise training has been deemed a beneficial treatment for obesity and insulin resistance. Furthermore, exercise is a feasible method to combat high-fat diet (HFD)-induced alterations in insulin sensitivity. The purpose of this study was to determine whether AMPK-α2 activity is required to gain beneficial effects of exercise training with high-fat feeding. Wild-type (WT) and AMPK-α2 dominant-negative (DN) male mice were fed standard diet (SD), underwent voluntary wheel running (TR), fed HFD, or trained with HFD (TR + HFD). By week 6, TR, irrespective of genotype, decreased blood glucose and increased citrate synthase activity in both diet groups and decreased insulin levels in HFD groups. Hindlimb perfusions were performed, and, in WT mice with SD, TR increased insulin-mediated palmitate uptake (76.7%) and oxidation (>2-fold). These training-induced changes were not observed in the DN mice. With HFD, TR decreased palmitate oxidation (61-64%) in both WT and DN and increased palmitate uptake (112%) in the WT with no effects on palmitate uptake in the DN. With SD, TR increased ERK1/2 and JNK1/2 phosphorylation, regardless of genotype. With HFD, TR reduced JNK1/2 phosphorylation, regardless of genotype, carnitine palmitoyltransferase 1 expression in WT, and CD36 expression in both DN and WT. These data suggest that low AMPK-α2 signaling disrupts, in part, the exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following HFD.
authors.affiliation: Department of Biological Sciences, Human and Evolutionary Biology Section, Dana and David Dornsife College of Arts, Letters, and Sciences, University of Southern California, Los Angeles, California; and Crean College of Health and Behavioral Sciences, Chapman University, Orange, California.
authors.forename: Marcia J
authors.initials: MJ
authors.lastname: Abbott
authors.affiliation: Department of Biological Sciences, Human and Evolutionary Biology Section, Dana and David Dornsife College of Arts, Letters, and Sciences, University of Southern California, Los Angeles, California; and turcotte@usc.edu.
authors.forename: Lorraine P
authors.initials: LP
authors.lastname: Turcotte
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism / Q000502:physiology; D018955:CD36 Antigens / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D059305:Diet, High-Fat / Q000379:methods; D006614:Hindlimb / Q000378:metabolism / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D018955:CD36 Antigens; D007328:Insulin; D010168:Palmitates; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase; D048056:Mitogen-Activated Protein Kinase 9; C534978:Prkaa2 protein, mouse; D048055:Mitogen-Activated Protein Kinase 8; D055372:AMP-Activated Protein Kinases
keywords: AMPK; exercise training; fatty acid metabolism; glucose uptake; insulin resistance