title: Skeletal muscle mitochondrial and metabolic responses to a high-fat diet in female rats bred for high and low aerobic capacity.
abstract: Rats selected artificially to be low-capacity runners (LCR) possess a metabolic syndrome phenotype that is worsened by a high-fat diet (HFD), whereas rats selected to be high-capacity runners (HCR) are protected against HFD-induced obesity and insulin resistance. This study examined whether protection against, or susceptibility to, HFD-induced insulin resistance in the HCR-LCR strains is associated with contrasting metabolic adaptations in skeletal muscle. HCR and LCR rats (generation 20; n = 5-6; maximum running distance approximately 1800 m vs. approximately 350 m, respectively (p < 0.0001)) were divided into HFD (71.6% energy from fat) or normal chow (NC) (16.7% energy from fat) groups for 7 weeks (from 24 to 31 weeks of age). Skeletal muscle (red gastrocnemius) mitochondrial-fatty acid oxidation (FAO), mitochondrial-enzyme activity, mitochondrial-morphology, peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), and peroxisome proliferator-activated receptor delta (PPARdelta) expression and insulin sensitivity (intraperitoneal glucose tolerance tests) were measured. The HFD caused increased adiposity and reduced insulin sensitivity only in the LCR and not the HCR strain. Isolated mitochondria from the HCR skeletal muscle displayed a 2-fold-higher rate of FAO on NC, but both groups increased FAO following HFD. PGC-1alpha mRNA expression and superoxide dismutase activity were significantly reduced with the HFD in the LCR rats, but not in the HCR rats. PPARdelta expression did not differ between strains or dietary conditions. These results do not provide a clear connection between protection of insulin sensitivity and HFD-induced adaptive changes in mitochondrial function or transcriptional responses but do not dismiss the possibility that elevated mitochondrial FAO in the HCR may play a protective role.
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Scott P
authors.initials: SP
authors.lastname: Naples
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Borengasser
authors.forename: R Scott
authors.initials: RS
authors.lastname: Rector
authors.forename: Grace M
authors.initials: GM
authors.lastname: Uptergrove
authors.forename: E Matthew
authors.initials: EM
authors.lastname: Morris
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Mikus
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Koch
authors.forename: Steve L
authors.initials: SL
authors.lastname: Britton
authors.forename: Jamal A
authors.initials: JA
authors.lastname: Ibdah
authors.forename: John P
authors.initials: JP
authors.lastname: Thyfault
mesh_terms: D000222:Adaptation, Physiological; D050154:Adiposity; D000375:Aging / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D004435:Eating; D004734:Energy Metabolism / Q000235:genetics; D017079:Exercise Tolerance / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D047494:PPAR delta / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; D047494:PPAR delta; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D013482:Superoxide Dismutase
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