title: Rhythmic diurnal gene expression in human adipose tissue from individuals who are lean, overweight, and type 2 diabetic.
abstract: OBJECTIVE
  Previous animal studies suggest a functional relationship between metabolism, type 2 diabetes, and the amplitude of daily rhythms in white adipose tissue (WAT). However, data interpretation is confounded by differences in genetic background and diet or limited sampling points. We have taken the novel approach of analyzing serial human WAT biopsies across a 24-h cycle in controlled laboratory conditions.
  
  
  METHODS
  Lean (n = 8), overweight/obese (n = 11), or overweight/obese type 2 diabetic (n = 8) volunteers followed a strict sleep-wake and dietary regimen for 1 week prior to the laboratory study. They were then maintained in controlled light-dark conditions in a semirecumbent posture and fed hourly during wake periods. Subcutaneous WAT biopsies were collected every 6 h over 24 h, and gene expression was measured by quantitative PCR.
  
  
  RESULTS
  Lean individuals exhibited significant (P < 0.05) temporal changes of core clock (PER1, PER2, PER3, CRY2, BMAL1, and DBP) and metabolic (REVERBα, RIP140, and PGC1α) genes. The BMAL1 rhythm was in approximate antiphase with the other clock genes. It is noteworthy that there was no significant effect (P > 0.05) of increased body weight or type 2 diabetes on rhythmic gene expression.
  
  
  CONCLUSIONS
  The robust nature of these rhythms and their relative phasing indicate that WAT now can be considered as a peripheral tissue suitable for the study of in vivo human rhythms. Comparison of data between subject groups clearly indicates that obesity and type 2 diabetes are not related to the amplitude of rhythmic WAT gene expression in humans maintained under controlled conditions.
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK.
authors.forename: Daniella T
authors.initials: DT
authors.lastname: Otway
authors.forename: Simone
authors.initials: S
authors.lastname: Mäntele
authors.forename: Silvia
authors.initials: S
authors.lastname: Bretschneider
authors.forename: John
authors.initials: J
authors.lastname: Wright
authors.forename: Paul
authors.initials: P
authors.lastname: Trayhurn
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Skene
authors.forename: M Denise
authors.initials: MD
authors.lastname: Robertson
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Johnston
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D000078723:Nuclear Receptor Interacting Protein 1; D009765:Obesity / Q000235:genetics*; D050177:Overweight / Q000235:genetics*; D056950:Period Circadian Proteins / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016133:Polymerase Chain Reaction; D013851:Thinness / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C538966:CRY2 protein, human; D056931:Cryptochromes; C063898:DBP protein, human; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; C539022:PER1 protein, human; C421902:PER2 protein, human; C512644:PER3 protein, human; C486497:PPARGC1A protein, human; D056950:Period Circadian Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors