title: A high-fat diet elicits differential responses in genes coordinating oxidative metabolism in skeletal muscle of lean and obese individuals.
abstract: BACKGROUND
  In lean individuals, increasing dietary lipid can elicit an increase in whole body lipid oxidation; however, with obesity the capacity to respond to changes in substrate availability appears to be compromised.
  
  
  OBJECTIVE
  To determine whether the responses of genes regulating lipid oxidation in skeletal muscle differed between lean and insulin resistant obese humans upon exposure to a high-fat diet (HFD).
  
  
  METHODS
  A 5-d prospective study conducted in the research unit of an academic center.
  
  
  METHODS
  Healthy, lean (n = 12; body mass index = 22.1 ± 0.6 kg/m(2)), and obese (n=10; body mass index = 39.6 ± 1.7 kg/m(2)) males and females, between ages 18 and 30.
  
  
  METHODS
  Participants were studied before and after a 5-d HFD (65% fat).
  
  
  METHODS
  Skeletal muscle biopsies (vastus lateralis) were obtained in the fasted and fed states before and after the HFD and mRNA content for genes involved with lipid oxidation determined. Skeletal muscle acylcarnitine content was determined in the fed states before and after the HFD.
  
  
  RESULTS
  Peroxisome proliferator activated receptor (PPAR) α mRNA content increased in lean, but not obese, subjects after a single high-fat meal. From Pre- to Post-HFD, mRNA content exhibited a body size × HFD interaction, where the lean individuals increased while the obese individuals decreased mRNA content for pyruvate dehydrogenase kinase 4, uncoupling protein 3, PPARα, and PPARγ coactivator-1α (P ≤ 0.05). In the obese subjects medium-chain acylcarnitine species tended to accumulate, whereas no change or a reduction was evident in the lean individuals.
  
  
  CONCLUSIONS
  These findings indicate a differential response to a lipid stimulus in the skeletal muscle of lean and insulin resistant obese humans.
authors.affiliation: Human Performance Laboratory, East Carolina University, Greenville, North Carolina 27858, USA. kristen.boyle@ucdenver.edu
authors.forename: K E
authors.initials: KE
authors.lastname: Boyle
authors.forename: J P
authors.initials: JP
authors.lastname: Canham
authors.forename: L A
authors.initials: LA
authors.lastname: Consitt
authors.forename: D
authors.initials: D
authors.lastname: Zheng
authors.forename: T R
authors.initials: TR
authors.lastname: Koves
authors.forename: T P
authors.initials: TP
authors.lastname: Gavin
authors.forename: D
authors.initials: D
authors.lastname: Holbert
authors.forename: P D
authors.initials: PD
authors.lastname: Neufer
authors.forename: O
authors.initials: O
authors.lastname: Ilkayeva
authors.forename: D M
authors.initials: DM
authors.lastname: Muoio
authors.forename: J A
authors.initials: JA
authors.lastname: Houmard
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics*; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000096:biosynthesis / Q000235:genetics; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D021241:Spectrometry, Mass, Electrospray Ionization; D000071247:Uncoupling Protein 3; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D012333:RNA, Messenger; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3; C116917:acylcarnitine; D030481:Pyruvate Dehydrogenase (Lipoamide); D002331:Carnitine