title: Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial.
abstract: OBJECTIVE
  To determine if caloric restriction (CR) would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I)).
  
  
  METHODS
  Forty-six volunteers were randomized to a weight maintenance diet (Control), 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX), or a liquid calorie diet (890 kcal/d until 15% reduction in body weight)for six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA), amino acids (AA), and acylcarnitines (AC). S(I) was measured with an intravenous glucose tolerance test.
  
  
  RESULTS
  Over three and six months, there were significantly larger differences in fasting-to-postprandial (FPP) concentrations of medium and long chain AC (byproducts of FA oxidation) in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P = 0.02; CR-6 month P = 0.002; CR+EX-3 month P = 0.09; CR+EX-6 month P = 0.08). After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P = 0.07; CR-3 month P = 0.08). Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying S(I) (P<0.05 for both).
  
  
  CONCLUSIONS
  Based on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in S(I).
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00099151.
authors.affiliation: Physical Medicine and Rehabilitation, Veterans Affairs Medical Center, Durham, North Carolina, United States of America. huffm007@mc.duke.edu
authors.forename: Kim M
authors.initials: KM
authors.lastname: Huffman
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Redman
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Landerman
authors.forename: Carl F
authors.initials: CF
authors.lastname: Pieper
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stevens
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Muehlbauer
authors.forename: Brett R
authors.initials: BR
authors.lastname: Wenner
authors.forename: James R
authors.initials: JR
authors.lastname: Bain
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Kraus
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.forename: Eric
authors.initials: E
authors.lastname: Ravussin
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood; D031204:Caloric Restriction; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood; D002149:Energy Intake / Q000502:physiology; D015444:Exercise / Q000502:physiology; D005215:Fasting / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000378:metabolism*; D019518:Postprandial Period; D025341:Principal Component Analysis
chemical_list: D000596:Amino Acids; D005230:Fatty Acids, Nonesterified; C116917:acylcarnitine; D002331:Carnitine