Clock genes shown to be associated with human metabolic syndrome
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The molecular basis of circadian rhythms comprises e.g. clock genes. These regulate 24-hour circadian rhythms in the brain, but clock genes may also be involved in circadian regulation of other organs, which possess internal genetic clocks. In animal experimental models, clock genes have been shown to play a role in adipose tissue (AT) physiology. The current study was designed to investigate the expression of several clock genes, Bmal1, Per2 and Cry1, in human AT and to elucidate whether these clock genes expressions were related to metabolic syndrome features. To this end, visceral and subcutaneous AT samples were obtained from 8 morbid obese men undergoing laparoscopic surgery due to obesity, biopsies were taken as paired samples at the beginning of the surgical procedure, metabolic syndrome features including insulin resistance (HOMA-IR) were assessed, and expression of the different clock genes, hBmal1, hPer2 and hCry1, was determined by quantitative real-time PCR. Clock genes were expressed in both AT depots, hBmal1 expression being significantly lower than hPer2 and hCry1 in both AT (P<0.001). Clock genes AT expression was associated with metabolic syndrome features: hPer2 expression level from visceral fat depot was inversely correlated to waist circumference (P<0.01), while the three clock genes were significantly and negatively correlated to total cholesterol and LDL cholesterol (P<0.01). Based on these data, the authors conclude that the association of clock genes with abdominal fat content and cardiovascular risk factors may indicate a potential role of these genes in human metabolic syndrome.
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