Aerobic training reverses high-fat diet-induced pro-inflammatory signalling in rat skeletal muscle.
High-fat feeding activates components of the pro-inflammatory pathway and increases co-immunoprecipitation of suppressor of cytokine signalling (SOCS)-3 with both the insulin receptor (IR)-β subunit and IRS-1, which together contribute to keeping PI-3 kinase from being fully activated. However, whether aerobic training reverses these impairments is unknown. Sprague-Dawley rats were fed a chow (CON, n = 8) or saturated high-fat (n = 16) diets for 4 weeks. High-fat-fed rats were then allocated (n = 8/group) to either sedentary (HF) or aerobic exercise training (HFX) for an additional 4 weeks after which all animals underwent hind limb perfusions. Insulin-stimulated red quadriceps 3-O-methylglucose transport rates and PI-3 kinase activity were greater (p < 0.05) in CON and HFX compared to HF. IRS-1 tyrosine phosphorylation was increased (p < 0.05) and IRS-1 serine 307 phosphorylation was decreased (p < 0.05) in HFX compared to HF. IR-β subunit co-immunoprecipitation with IRS-1 was increased in HFX compared to HF. SOCS-3 co-immunoprecipitation with both the IR-β subunit and IRS-1 was decreased (p < 0.05) in HFX compared to HF. IKKα/β serine phosphorylation, and IκBα serine phosphorylation were decreased (p < 0.05) while IκBα protein concentration was increased in HFX compared to HF. By decreasing the association of SOCS-3 with both the IR-β subunit and IRS-1 the interaction between IRS-1 and the IR-β subunit was normalized in the HFX, and may have contributed to skeletal muscle PI-3 kinase being fully activated by insulin. Additionally, the reduction in IKKα/β serine phosphorylation in HFX may have contributed to decreasing IRS-1 serine phosphorylation, and in turn, promoted the normalization of insulin-stimulated activation of PI-3 kinase.
Yaspelkis
Ben B
BB
Exercise Biochemistry Laboratory, Department of Kinesiology, California State University Northridge, 18111 Nordhoff Street, Northridge, CA 91330-8287, USA. ben.yaspelkis@csun.edu
Kvasha
Ilya A
IA
Lessard
Sarah J
SJ
Rivas
Donato A
DA
Hawley
John A
JA
D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology*; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000276:immunology* / Q000378:metabolism; D009220:Myositis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000072000:NF-KappaB Inhibitor alpha; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000276:immunology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000276:immunology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
D004041:Dietary Fats; D020672:I-kappa B Proteins; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C000606206:Nfkbia protein, rat; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000072000:NF-KappaB Inhibitor alpha; D019869:Phosphatidylinositol 3-Kinases; D051550:I-kappa B Kinase