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.
Highlights
Circadian clocks regulate 24 hours rhythms in physiology and behavior that are essential to maintaining normal metabolic function
PPARG2 expression levels were increased in SC from obese subjects (Fig. 4I) whereas NAMPT gene expression levels were similar (Fig. 4J) in both groups. These results indicate that the changes in PER2, CRY1 and ROR ALPHA from obese subjects were unique for the stromal cells fraction, whereas changes in CRY2 and REV-ERB ALPHA occurred in adipocytes, stromal cells and visceral adipose tissue (VAT)
This study provides the first evidence of altered clock gene expression in visceral adipose from obese subjects
Summary
Circadian clocks regulate 24 hours rhythms in physiology and behavior that are essential to maintaining normal metabolic function. Disruption of circadian rhythms (e.g., shift work) is associated with increased adiposity and increased risk of obesity and type 2 diabetes [1,2]. Recent studies have linked polymorphisms of human circadian clock genes with metabolic dysfunction [3,4]. In a single time point study, clock gene expression was associated with different components of metabolic syndrome in human adipose tissue [6]. It is of extreme importance to identify which clock genes are disrupted in obesity for an optimization of clinical interventions aimed at reducing the incidence of metabolic diseases such as type 2 diabetes
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