Tom, Robby ZachariahGarcía-Roves, Pablo M. (Pablo Miguel)Sjögren, Rasmus J. O.Jiang, Lake Q.Holmström, Maria H.Deshmukh, Atul S.Vieira, ElaineChibalin, Alexander V.Björnholm, MarieZierath, Juleen R.2019-06-132019-06-132014-050012-1797https://hdl.handle.net/2445/135010AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (α) and two regulatory subunits (β and γ), which act as a metabolic sensor to regulate glucose and lipid metabolism. A mutation in the γ3 subunit (AMPKγ3(R225Q)) increases basal AMPK phosphorylation, while concomitantly reducing sensitivity to AMP. AMPKγ3(R225Q) (γ3(R225Q)) transgenic mice are protected against dietary-induced triglyceride accumulation and insulin resistance. We determined whether skeletal muscle-specific expression of AMPKγ3(R225Q) prevents metabolic abnormalities in leptin-deficient ob/ob (ob/ob-γ3(R225Q)) mice. Glycogen content was increased, triglyceride content was decreased, and diacylglycerol and ceramide content were unaltered in gastrocnemius muscle from ob/ob-γ3(R225Q) mice, whereas glucose tolerance was unaltered. Insulin-stimulated glucose uptake in extensor digitorum longus muscle during the euglycemic-hyperinsulinemic clamp was increased in lean γ3(R225Q) mice, but not in ob/ob-γ3(R225Q) mice. Acetyl-CoA carboxylase phosphorylation was increased in gastrocnemius muscle from γ3(R225Q) mutant mice independent of adiposity. Glycogen and triglyceride content were decreased after leptin treatment (5 days) in ob/ob mice, but not in ob/ob-γ3(R225Q) mice. In conclusion, metabolic improvements arising from muscle-specific expression of AMPKγ3(R225Q) are insufficient to ameliorate insulin resistance and obesity in leptin-deficient mice. Central defects due to leptin deficiency may override any metabolic benefit conferred by peripheral overexpression of the AMPKγ3(R225Q) mutation.12 p.application/pdfengcc-by-nc-nd (c) American Diabetes Association, 2014http://creativecommons.org/licenses/by-nc-nd/3.0/esMetabolismeResistència a la insulinaFisiologiaLeptinaGenèticaMúsculsEsqueletObesitatRatolins (Animals de laboratori)MetabolismInsulin resistancePhysiologyLeptinGeneticsMusclesSkeletonObesityMice (Laboratory animals)info:eu-repo/semantics/article6505162019-06-13info:eu-repo/semantics/openAccess24487023