title: High-fat feeding inhibits exercise-induced increase in mitochondrial respiratory flux in skeletal muscle.
abstract: Twenty one healthy untrained male subjects were randomized to follow a high-fat diet (HFD; 55-60E% fat, 25-30E% carbohydrate, and 15E% protein) or a normal diet (ND; 25-35E% fat, 55-60E% carbohydrate, and 10-15E% protein) for 2(1/2) wk. Diets were isocaloric and tailored individually to match energy expenditure. At 2(1/2) wk of diet, one 60-min bout of bicycle exercise (70% of maximal oxygen uptake) was performed. Muscle biopsies were obtained before and after the diet, immediately after exercise, and after 3-h recovery. Insulin sensitivity (hyperinsulinemic-euglycemic clamp) and intramyocellular triacylglycerol content did not change with the intervention in either group. Indexes of mitochondrial density were similar across the groups and intervention. Mitochondrial respiratory rates, measured in permeabilized muscle fibers, showed a 31 ± 11 and 26 ± 9% exercise-induced increase (P < 0.05) in state 3 (glycolytic substrates) and uncoupled respiration, respectively. However, in HFD this increase was abolished. At recovery, no change from resting respiration was seen in either group. With a lipid substrate (octanoyl-carnitine with or without ADP), similar exercise-induced increases (31-62%) were seen in HFD and ND, but only in HFD was an elevated (P < 0.05) respiratory rate seen at recovery. With HFD complex I and IV protein expression decreased (P < 0.05 and P = 0.06, respectively). A fat-rich diet induces marked changes in the mitochondrial electron transport system protein content and in exercise-induced mitochondrial substrate oxidation rates, with the effects being present hours after the exercise. The effect of HFD is present even without effects on insulin sensitivity and intramyocellular lipid accumulation. An isocaloric high-fat diet does not cause insulin resistance.
authors.affiliation: Xlab, Center for Healthy Aging, Dept. of Biomedical Sciences, Faculty of Health Sciences, Bldg. 12.4.7, Univ. of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Skovbro
authors.forename: Robert
authors.initials: R
authors.lastname: Boushel
authors.forename: Christina Neigaard
authors.initials: CN
authors.lastname: Hansen
authors.forename: Jørn Wulff
authors.initials: JW
authors.lastname: Helge
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela
mesh_terms: D000328:Adult; D001481:Basal Metabolism; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D019069:Cell Respiration; D003718:Denmark; D004041:Dietary Fats / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D002149:Energy Intake; D004734:Energy Metabolism; D015444:Exercise; D015309:Glucose Clamp Technique; D006019:Glycolysis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D014280:Triglycerides; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I