title: Diurnal variation in insulin sensitivity of glucose metabolism is associated with diurnal variations in whole-body and cellular fatty acid metabolism in metabolically normal women.
abstract: BACKGROUND
  The mechanism(s) responsible for diurnal variations in insulin sensitivity of glucose metabolism in healthy people are unclear.
  
  
  OBJECTIVE
  The objective of the study was to evaluate whether diurnal variations in whole-body and cellular fatty acid metabolism could contribute to evening insulin resistance in metabolically normal people.
  
  
  METHODS
  We measured plasma the free fatty acid (FFA) concentration, palmitate kinetics, and skeletal muscle expression of genes involved in fatty acid metabolism at breakfast (7:00 am) and dinner (7:00 pm) in 13 overweight (body mass index 27.8 ± 1.2 kg/m(2)) but metabolically normal, women.
  
  
  RESULTS
  Plasma FFA concentration was approximately 30% greater just before consuming dinner than breakfast (P < .05) and remained greater after dinner than breakfast (FFA areas under the curve: 0.88 ± 0.33 and 0.51 ± 0.09 μmol/mL × 4 h, P = .001). However, adipose tissue lipolytic activity was not different in the evening and in the morning. Skeletal muscle expression of genes that regulate fatty acid oxidation were 38-82% lower, whereas genes involved in de novo lipogenesis were 51%-87 % higher before dinner than before breakfast (all P < .05), and these changes were associated with diurnal variation in the muscle expression of core clock genes that regulate fatty acid metabolism.
  
  
  CONCLUSIONS
  Metabolically normal women demonstrate diurnal variations in fatty acid metabolism, manifested by an increase in circulating FFAs, presumably derived from previous meal consumption rather than lipolysis of adipose tissue triglycerides, and a shift in muscle fatty acid metabolism from oxidation to lipogenesis. These metabolic alterations could be responsible for the known evening decline in insulin sensitivity.
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine (J.Y., P.A.-V., B.W.P., A.L.O., S.I., B.M., S.K.) and Department of Developmental Biology (S.I.), Washington University School of Medicine, St Louis, Missouri 63110.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshino
authors.forename: Paloma
authors.initials: P
authors.lastname: Almeda-Valdes
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Patterson
authors.forename: Adewole L
authors.initials: AL
authors.lastname: Okunade
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Imai
authors.forename: Bettina
authors.initials: B
authors.lastname: Mittendorfer
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D004435:Eating / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050155:Lipogenesis / Q000502:physiology; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D050177:Overweight / Q000378:metabolism*; D010168:Palmitates / Q000493:pharmacokinetics; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010168:Palmitates; D006854:Hydrocortisone