title: Skeletal muscle AMP-activated protein kinase γ1(H151R) overexpression enhances whole body energy homeostasis and insulin sensitivity.
abstract: AMP-activated protein kinase (AMPK) is a major sensor of energy homeostasis and stimulates ATP-generating processes such as lipid oxidation and glycolysis in peripheral tissues. The heterotrimeric enzyme consists of a catalytic α-subunit, a β-subunit that is important for enzyme activity, and a noncatalytic γ-subunit that binds AMP and activates the AMPK complex. We generated a skeletal muscle Cre-inducible transgenic mouse model expressing a mutant γ1-subunit (AMPKγ1(H151R)), resulting in chronic AMPK activation. The expression of the predominant AMPKγ3 isoform in skeletal muscle was reduced in extensor digitorum longus (EDL) muscle (81-83%) of AMPKγ1(H151R) transgenic mice, whereas the abundance and phosphorylation of the AMPK target acetyl-CoA carboxylase was increased in tibialis anterior muscle. Glycogen content was increased 10-fold in gastrocnemius muscle. Whole body carbohydrate oxidation was increased by 11%, and whereas glucose tolerance was unaffected, insulin sensitivity was increased in AMPKγ1(H151R) transgenic mice. Furthermore, perigonadal white adipose tissue mass and serum leptin were reduced in female AMPKγ1(H151R) transgenic mice by 38 and 51% respectively. Conversely, in male AMPKγ1(H151R) transgenic mice, food intake was increased (14%), but body weight and body composition were unaltered, presumably because of increased energy expenditure. In conclusion, transgenic activation of skeletal muscle AMPKγ1 in this model plays an important sex-specific role in skeletal muscle metabolism and whole body energy homeostasis.
authors: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;
authors: Milena
authors: M
authors: Schönke
authors: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; and.
authors: Martin G
authors: MG
authors: Myers
authors: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors: Juleen R
authors: JR
authors: Zierath
authors: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; marie.bjornholm@ki.se.
authors: Marie
authors: M
authors: Björnholm
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D006639:Histidine / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000201:enzymology*; D020125:Mutation, Missense; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
chemical_list: C526224:Prkag1 protein, mouse; D006639:Histidine; D001120:Arginine; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; metabolism; skeletal muscle