title: Altered clock gene expression in obese visceral adipose tissue is associated with metabolic syndrome.
abstract: Clock gene expression was associated with different components of metabolic syndrome (MS) in human adipose tissue. However, no study has been done to compare the expression of clock genes in visceral adipose tissue (VAT) from lean and obese subjects and its clinical implications. Therefore, we studied in lean and obese women the endogenous 24 h expression of clock genes in isolated adipocytes and its association with MS components. VAT was obtained from lean (BMI 21-25 kg/m2; n = 21) and morbidly obese women (BMI >40 kg/m2; n = 28). The 24 h pattern of clock genes was analyzed every 6 hours using RT-PCR. Correlation of clinical data was studied by Spearman analysis. The 24 h pattern of clock genes showed that obesity alters the expression of CLOCK, BMAL1, PER1, CRY2 and REV-ERB ALPHA in adipocytes with changes found in CRY2 and REV-ERB ALPHA throughout the 24 h period. The same results were confirmed in VAT and stromal cells (SC) showing an upregulation of CRY2 and REV-ERB ALPHA from obese women. A positive correlation was observed for REV-ERB ALPHA gene expression with BMI and waist circumference in the obese population. Expression of ROR ALPHA was correlated with HDL levels and CLOCK with LDL. Obese subjects with MS exhibited positive correlation in the PER2 gene with LDL cholesterol, whereas REV-ERB ALPHA was correlated with waist circumference. We identified CRY2 and REV-ERB ALPHA as the clock genes upregulated in obesity during the 24 h period and that REV-ERB ALPHA is an important gene associated with MS.
authors.affiliation: CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Diabetes and Obesity Research Laboratory, IDIBAPS, Barcelona, Spain.
authors.forename: Elaine
authors.initials: E
authors.lastname: Vieira
authors.affiliation: CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Diabetes and Obesity Research Laboratory, IDIBAPS, Barcelona, Spain.
authors.forename: Elena g
authors.initials: Eg
authors.lastname: Ruano
authors.affiliation: Diabetes and Obesity Research Laboratory, IDIBAPS, Barcelona, Spain.
authors.forename: Ana Lucia C
authors.initials: AL
authors.lastname: Figueroa
authors.affiliation: CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Aranda
authors.affiliation: Department of Gastrointestinal Surgery, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Dulce
authors.initials: D
authors.lastname: Momblan
authors.affiliation: Institute Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; Faculty of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Carmona
authors.affiliation: CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Diabetes and Obesity Research Laboratory, IDIBAPS, Barcelona, Spain; Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain; Faculty of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Gomis
authors.affiliation: CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Diabetes and Obesity Research Laboratory, IDIBAPS, Barcelona, Spain; Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain; Faculty of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Vidal
authors.affiliation: CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Diabetes and Obesity Research Laboratory, IDIBAPS, Barcelona, Spain; Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain.
authors.forename: Felicia A
authors.initials: FA
authors.lastname: Hanzu
mesh_terms: D000328:Adult; D057906:Circadian Clocks; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000378:metabolism* / Q000473:pathology