title: Increasing dietary fat elicits similar changes in fat oxidation and markers of muscle oxidative capacity in lean and obese humans.
abstract: In lean humans, increasing dietary fat intake causes an increase in whole-body fat oxidation and changes in genes that regulate fat oxidation in skeletal muscle, but whether this occurs in obese humans is not known. We compared changes in whole-body fat oxidation and markers of muscle oxidative capacity differ in lean (LN) and obese (OB) adults exposed to a 2-day high-fat (HF) diet. Ten LN (BMI = 22.5±2.5 kg/m², age = 30±8 yrs) and nine OB (BMI = 35.9±4.93 kg/m², 38±5 yrs, Mean±SD) were studied in a room calorimeter for 24hr while consuming isocaloric low-fat (LF, 20% of energy) and HF (50% of energy) diets. A muscle biopsy was obtained the next morning following an overnight fast. 24h respiratory quotient (RQ) did not significantly differ between groups (LN: 0.91±0.01; OB: 0.92±0.01) during LF, and similarly decreased during HF in LN (0.86±0.01) and OB (0.85±0.01). The expression of pyruvate dehydrogenase kinase 4 (PDK4) and the fatty acid transporter CD36 increased in both LN and OB during HF. No other changes in mRNA or protein were observed. However, in both LN and OB, the amounts of acetylated peroxisome proliferator-activated receptor γ coactivator-1-α (PGC1-α) significantly decreased and phosphorylated 5-AMP-activated protein kinase (AMPK) significantly increased. In response to an isoenergetic increase in dietary fat, whole-body fat oxidation similarly increases in LN and OB, in association with a shift towards oxidative metabolism in skeletal muscle, suggesting that the ability to adapt to an acute increase in dietary fat is not impaired in obesity.
authors.affiliation: Center for Human Nutrition, School of Medicine, University of Colorado Denver, Denver, Colorado, United States of America.
authors.forename: Audrey
authors.initials: A
authors.lastname: Bergouignan
authors.forename: Wendolyn S
authors.initials: WS
authors.lastname: Gozansky
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Barry
authors.forename: Wayne
authors.initials: W
authors.lastname: Leitner
authors.forename: Paul S
authors.initials: PS
authors.lastname: MacLean
authors.forename: James O
authors.initials: JO
authors.lastname: Hill
authors.forename: Boris
authors.initials: B
authors.lastname: Draznin
authors.forename: Edward L
authors.initials: EL
authors.lastname: Melanson
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002151:Calorimetry; D004041:Dietary Fats / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D013851:Thinness / Q000097:blood / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D005227:Fatty Acids; D009124:Muscle Proteins; D014280:Triglycerides