title: Early skeletal muscle adaptations to short-term high-fat diet in humans before changes in insulin sensitivity.
abstract: OBJECTIVE
  The purpose of this investigation was to understand the metabolic adaptations to a short-term (5 days), isocaloric, high-fat diet (HFD) in healthy, young males.
  
  
  METHODS
  Two studies were undertaken with 12 subjects. Study 1 investigated the effect of the HFD on skeletal muscle substrate metabolism and insulin sensitivity. Study 2 assessed the metabolic and transcriptional responses in skeletal muscle to the transition from a fasted to fed state using a high-fat meal challenge before and after 5 days of the HFD.
  
  
  RESULTS
  Study 1 showed no effect of a HFD on skeletal muscle metabolism or insulin sensitivity in fasting samples. Study 2 showed that a HFD elicits significant increases in fasting serum endotoxin and disrupts the normal postprandial excursions of serum endotoxin, as well as metabolic and transcriptional responses in skeletal muscle. These effects after 5 days of the HFD were accompanied by an altered fasting and postprandial response in the ratio of phosphorylated- to total-p38 protein. These changes all occurred in the absence of alterations in insulin sensitivity.
  
  
  CONCLUSIONS
  Our findings provide evidence for early biological adaptations to high-fat feeding that proceed and possibly lead to insulin resistance.
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
authors.forename: Angela S
authors.initials: AS
authors.lastname: Anderson
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Haynie
authors.forename: Ryan P
authors.initials: RP
authors.lastname: McMillan
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Osterberg
authors.forename: Nabil E
authors.initials: NE
authors.lastname: Boutagy
authors.forename: Madlyn I
authors.initials: MI
authors.lastname: Frisard
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Davy
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Davy
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Hulver
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D019518:Postprandial Period; D055815:Young Adult
chemical_list: D004041:Dietary Fats
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