title: Clock genes are implicated in the human metabolic syndrome.
abstract: BACKGROUND
  Clock genes play a role in adipose tissue (AT) in animal experimental models. However, it remains to be elucidated whether these genes are expressed in human AT.
  
  
  OBJECTIVE
  We investigated the expression of several clock genes, Bmal1, Per2 and Cry1, in human AT from visceral and subcutaneous abdominal depots. A second objective was to elucidate whether these clock genes expressions were related to the metabolic syndrome features.
  
  
  METHODS
  Visceral and subcutaneous AT samples were obtained from morbid obese men (n=8), age: 42+/-13 years and body mass index>/=40 kg/m(2), undergoing laparoscopic surgery due to obesity. Biopsies were taken as paired samples at the beginning of the surgical process (1100 hour). Metabolic syndrome features such as waist circumference, plasma glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein (LDL) cholesterol were also studied. Homeostasis model assessment index of insulin resistance was also calculated. The expression of the different clock genes, hBmal1, hPer2 and hCry1, was determined by quantitative real-time PCR.
  
  
  RESULTS
  Clock genes were expressed in both human AT depots. hBmal1 expression was significantly lower than hPer2 and hCry1 in both AT (P<0.001). All genes were highly correlated to one another in the subcutaneous fat, while no correlation was found between Bmal1 and Per2 in the visceral AT. Clock genes AT expression was associated with the metabolic syndrome parameters: hPer2 expression level from visceral depot was inversely correlated to waist circumference (P<0.01), while the three clock genes studied were significantly and negatively correlated to total cholesterol and LDL cholesterol (P<0.01).
  
  
  CONCLUSIONS
  We have demonstrated for the first time in humans that clock genes are expressed in both subcutaneous and visceral fat. Their association with abdominal fat content and cardiovascular risk factors may be an indicator of the potential role of these clock genes in the metabolic syndrome disturbances.
authors.affiliation: Department of Physiology, University of Murcia, Murcia, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Gómez-Abellán
authors.forename: J J
authors.initials: JJ
authors.lastname: Hernández-Morante
authors.forename: J A
authors.initials: JA
authors.lastname: Luján
authors.forename: J A
authors.initials: JA
authors.lastname: Madrid
authors.forename: M
authors.initials: M
authors.lastname: Garaulet
mesh_terms: D056930:ARNTL Transcription Factors; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001683:Biological Clocks / Q000235:genetics; D056931:Cryptochromes; D005420:Flavoproteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D050152:Intra-Abdominal Fat / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D009767:Obesity, Morbid / Q000235:genetics* / Q000503:physiopathology; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050507:Subcutaneous Fat, Abdominal / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056931:Cryptochromes; D005420:Flavoproteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C538960:BMAL1 protein, human; C538963:CRY1 protein, human; C421902:PER2 protein, human