Altered clock gene expression in obese visceral adipose tissue is associated with metabolic syndrome

PLoS One. 2014 Nov 3;9(11):e111678. doi: 10.1371/journal.pone.0111678. eCollection 2014.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Circadian Clocks*
  • Female
  • Gene Expression Regulation*
  • Humans
  • Intra-Abdominal Fat / metabolism*
  • Intra-Abdominal Fat / pathology
  • Metabolic Syndrome / metabolism*
  • Metabolic Syndrome / pathology
  • Obesity / metabolism*
  • Obesity / pathology

Grants and funding

This work was sponsored by the Spanish Ministry of Economy and Competitiveness under grant agreement number PI13/01500 and by the Government of Catalonia under grant agreement number 2014SGR659. The work was conducted at the Centre Esther Koplowitz, Barcelona; CIBERDEM is an initiative of the Instituto de Salud Carlos III. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.