Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Arch Med Sci. 2011 Dec 31;7(6):933-40. doi: 10.5114/aoms.2011.26603. Epub 2011 Dec 30.
The aim of this study was to investigate the association between the variation in expression profile of clock genes and obesity using peripheral blood mononuclear (PMN) cells.
The subjects comprised 10 obese patients and 10 healthy volunteers. Blood was collected at different time-points during the day and levels of blood sugar, IRI, adiponectin and leptin were determined. Peripheral blood mononuclear cells were sampled, and expression levels of brain and muscle Arnt-like protein-1 (BMAL1), Period (PER)1, PER2, Cryptochrome (CRY)1, CRY2, and REV-ERBα mRNA were quantified.
During the day, the expression levels of BMAL1, CRY1, CRY2 and PER2 genes in PMN cells of the obese group were all significantly higher compared to those in the non-obese group. In addition, expression of BMAL1, CRY1, CRY2 and PER2 genes in PMN cells increased between 12:00 and 21:00 in the obese group. In PMN cells of both groups, PER1 gene expression showed a bimodal pattern, with high expression at 9:00 and 18:00.
Differences were observed in the expression profile variation of clock genes between the obese and non-obese groups. This study reveals the differences in clock gene expression profiles between obese and non-obese subjects, with evidence for two distinct chronotypes, and suggests a contribution of these chronotypes to fat accumulation in humans.
本研究旨在通过外周血单个核细胞(PMNC)研究时钟基因表达谱的变化与肥胖之间的关系。
研究对象包括 10 名肥胖患者和 10 名健康志愿者。在一天中的不同时间点采集血液,并测定血糖、IRI、脂联素和瘦素水平。采集外周血单个核细胞,定量检测脑和肌肉芳香烃受体核转录因子样蛋白-1(BMAL1)、周期蛋白(PER)1、PER2、隐花色素(CRY)1、CRY2 和 REV-ERBαmRNA 的表达水平。
白天,肥胖组 PMN 细胞中 BMAL1、CRY1、CRY2 和 PER2 基因的表达水平均明显高于非肥胖组。此外,肥胖组 PMN 细胞中 BMAL1、CRY1、CRY2 和 PER2 基因的表达在 12:00 至 21:00 之间增加。在两组 PMN 细胞中,PER1 基因表达呈双峰模式,9:00 和 18:00 时表达较高。
肥胖组和非肥胖组时钟基因表达谱的变化存在差异。本研究揭示了肥胖和非肥胖个体时钟基因表达谱的差异,存在两种不同的生物钟类型,并提示这些生物钟类型可能与人类脂肪积累有关。