title: Effects of a brief high-fat diet and acute exercise on the mTORC1 and IKK/NF-κB pathways in rat skeletal muscle.
abstract: One exercise session can improve subsequent insulin-stimulated glucose uptake by skeletal muscle in healthy and insulin-resistant individuals. Our first aim was to determine whether a brief (2 weeks) high-fat diet (HFD) that caused muscle insulin resistance would activate the mammalian target of rapamycin complex 1 (mTORC1) and/or inhibitor of κB kinase/nuclear factor κB (IKK/NF-κB) pathways, which are potentially linked to induction of insulin resistance. Our second aim was to determine whether acute exercise that improved insulin-stimulated glucose uptake by muscles would attenuate activation of these pathways. We compared HFD-fed rats with rats fed a low-fat diet (LFD). Some animals from each diet group were sedentary and others were studied 3 h postexercise, when insulin-stimulated glucose uptake was increased. The results did not provide evidence that brief HFD activated either the mTORC1 (including phosphorylation of mTOR(Ser2448), TSC2(Ser939), p70S6K(Thr412), and RPS6(Ser235/236)) or the IKK/NF-κB (including abundance of IκBα or phosphorylation of NF-κB(Ser536), IKKα/β(Ser177/181), and IκB(Ser32)) pathway in insulin-resistant muscles. Exercise did not oppose the activation of either pathway, as evidenced by no attenuation of phosphorylation of key proteins in the IKK/NF-κB pathway (NF-κB(Ser536), IKKα/β(Ser177/181), and IκB(Ser32)), unaltered IκBα abundance, and no attenuation of phosphorylation of key proteins in the mTORC1 pathway (mTOR(Ser2448), TSC2(Ser939), and RPS6(Ser235/236)). Instead, exercise induced greater phosphorylation of 2 proteins of the mTORC1 pathway (PRAS40(Thr246) and p70S6K(Thr412)) in insulin-stimulated muscles, regardless of diet. Insulin resistance induced by a brief HFD was not attributable to greater activation of the mTORC1 or the IKK/NF-κB pathway in muscle, and exercise-induced improvement in insulin sensitivity was not attributable to attenuated activation of these pathways in muscle.
authors.affiliation: Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, MI 48109-2214, USA.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Castorena
authors.forename: Edward B
authors.initials: EB
authors.lastname: Arias
authors.forename: Naveen
authors.initials: N
authors.lastname: Sharma
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Cartee
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003065:Coenzyme A / Q000145:classification / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000097:blood; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D046912:Multiprotein Complexes; D009124:Muscle Proteins; D016328:NF-kappa B; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D003065:Coenzyme A
keywords: Akt; activité physique; inflammation; insulin resistance; insulinorésistance; obesity; obésité; physical activity