title: Acute effects of different diet compositions on skeletal muscle insulin signalling in obese individuals during caloric restriction.
abstract: OBJECTIVE
  The cellular effects of restricting fat versus carbohydrate during a low-calorie diet are unclear. The aim of this study was to examine acute effects of energy and macronutrient restriction on skeletal muscle insulin signalling in obesity.
  
  
  METHODS
  Eighteen obese individuals without diabetes underwent euglycemic-hyperinsulinemic clamp and skeletal muscle biopsy after: (a) 5days of eucaloric diet (30% fat, 50% carbohydrate), and (b) 5days of a 30% calorie-restricted diet, either low fat/high carbohydrate (LF/HC: 20% fat, 60% carbohydrate) or high-fat/low carbohydrate (HF/LC: 50% fat, 30% carbohydrate).
  
  
  RESULTS
  Weight, body composition, and insulin sensitivity were similar between groups after eucaloric diet. Weight loss was similar between groups after hypocaloric diet, 1.3±1.3kg (p<0.0001 compared with eucaloric). Whole-body insulin sensitivity was unchanged after calorie restriction and similar between groups. However, ex vivo skeletal muscle insulin signalling differed depending on macronutrient composition of calorie-restricted diet. Skeletal muscle of the LF/HC group had increased insulin-stimulated tyrosine phosphorylation of IRS-1, decreased insulin-stimulated Ser307 phosphorylation of IRS-1, and increased IRS-1-associated phosphatidylinositol (PI)3-kinase activity. Conversely, insulin stimulation of tyrosine phosphorylated IRS-1 was absent and serine 307 phosphorylation of IRS-1 was increased on HF/LC, with blunting of IRS-1-associated PI3-kinase activity.
  
  
  CONCLUSIONS
  Acute caloric restriction with an LF/HC diet alters skeletal muscle insulin signalling in a way that improves insulin sensitivity, while acute caloric restriction with an HF/LC diet induces changes compatible with insulin resistance. In both cases, ex vivo changes in skeletal muscle insulin signalling appear prior to changes in whole body insulin sensitivity.
authors.affiliation: Research Service, Department of Veterans Affairs, Denver, Colorado, USA. Cecilia.Wang@ucdenver.edu
authors.forename: Cecilia C L
authors.initials: CC
authors.lastname: Wang
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Adochio
authors.forename: J Wayne
authors.initials: JW
authors.lastname: Leitner
authors.forename: Ian M
authors.initials: IM
authors.lastname: Abeyta
authors.forename: Boris
authors.initials: B
authors.lastname: Draznin
authors.forename: Marc-Andre
authors.initials: MA
authors.lastname: Cornier
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000502:physiology; D015153:Blotting, Western; D031204:Caloric Restriction; D004032:Diet; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D019869:Phosphatidylinositol 3-Kinases