title: The acute effects of time-of-day-dependent high fat feeding on whole body metabolic flexibility in mice.
abstract: Both circadian disruption and timing of feeding have important roles in the development of metabolic disease. Despite growing acceptance that the timing of food consumption has long-term impact on metabolic homeostasis, little is known regarding the immediate influence on whole body metabolism, or the mechanisms involved. We aimed to examine the acute effects of time-of-day-dependent high fat feeding on whole body substrate metabolism and metabolic plasticity, and to determine the potential contribution of the adipocyte circadian clock.
  
  
  
  Mice were fed a regimen of 4-h meal at the beginning and end of the dark (waking) cycle, separated by 4 h of fasting. Daily experimental conditions consisted of either an early very high fat or high fat (EVHF or EHF, 60 or 45% kcals from fat, respectively) or late (LVHF or LHF) meal, paired with a low fat (LF, 10% kcals from fat) meal. Metabolic parameters, glucose tolerance, body fat composition and weight were assessed. To determine the role of the adipocyte circadian clock, an aP2-CLOCK mutant (ACM) mouse model was used.
  
  
  
  Mice in the EVHF or EHF groups showed a 13.2 or 8.84 higher percentage of caloric intake from fat and had a 0.013 or 0.026 lower daily average respiratory exchange ratio, respectively, compared with mice eating the opposite feeding regime. Changes in glucose tolerance, body fat composition and weight were not significant at the end of the 9-day restricted feeding period. ACM mice did not exhibit different metabolic responses to the feeding regimes compared with wild-type littermates. Circadian clock disruption did not influence the short-term response to timed feeding.
  
  
  
  Both the total fat composition of diet and the timing of fat intake may differentially mediate the effect of timed feeding on substrate metabolism, but may not induce acute changes in metabolic flexibility.
authors.affiliation: Department of Nutritional Sciences, University of Texas at Austin, Austin, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Joo
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Cox
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Kindred
authors.affiliation: Department of Nutritional Sciences, University of Texas at Austin, Austin, TX, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Lashinger
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Young
authors.affiliation: Department of Nutritional Sciences, University of Texas at Austin, Austin, TX, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Bray
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D057906:Circadian Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D002149:Energy Intake; D004734:Energy Metabolism / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D005508:Food Deprivation; D005951:Glucose Tolerance Test; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013997:Time Factors; D015430:Weight Gain
chemical_list: D001786:Blood Glucose