Regulation of the clock gene expression in human adipose tissue by weight loss
Regulation of the clock gene expression in human adipose tissue by weight loss
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DOI：
10.1038/ijo.2016.34
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发表时间：
2016-06-01
影响因子：
4.9
通讯作者：
Pfeiffer, A. F. H.
中科院分区：
文献类型：
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作者：
Pivovarova, O.;Goegebakan, O.;Pfeiffer, A. F. H.
背景：生物钟协调许多代谢过程，以适应对光暗和喂养方案的生理反应，并且生物钟本身受到代谢信号的调节。生物钟对能量平衡和体重调节的影响在啮齿类动物中得到了广泛研究，但在人类中却尚未得到广泛研究。在这里，我们研究了 (1) 人类脂肪组织中时钟基因的表达是否因体重减轻而改变，以及 (2) 这些改变是否与代谢参数相关。 受试者/方法：在每天同一时间进行 800 kcal 低热量饮食（加上每天 200 g 蔬菜）的减肥前后 8 周，收集皮下脂肪组织 (SAT) 样本。选择 50 名超重受试者参加研究，他们在 8 周后体重减轻了至少 8%。采用实时定量PCR法测定脂肪组织中10个时钟基因以及关键代谢和炎症基因的表达量。结果：减重后核心时钟基因PER2和NR1D1的表达量增加。经多重测试校正后，发现 PERIOD 表达与体重指数 (BMI) 和血清总胆固醇、高密度脂蛋白和低密度脂蛋白 (LDL) 胆固醇水平以及 NR1D1 表达与总胆固醇和 LDL 胆固醇的相关性变得不显着。时钟基因表达水平及其减肥引起的变化彼此密切相关，并与参与脂肪代谢（FASN、CPT1A、LPL、PPARG、PGC1A、ADIPOQ）、能量代谢（SIRT1）、自噬（LC3A、LC3B）和炎症反应（NFKB1、NFKBIA、NLRP3、 EMR1). 结论：人类 SAT 中的时钟基因表达受体重变化调节，并与 BMI、血清胆固醇水平以及代谢和炎症基因的表达相关。我们的数据证实了分子钟与代谢和炎症途径之间的紧密串扰，这些途径涉及使脂肪组织代谢适应人类能量摄入的变化。
BACKGROUND: The circadian clock coordinates numerous metabolic processes to adapt physiological responses to light-dark and feeding regimens and is itself regulated by metabolic cues. The implication of the circadian clock in the regulation of energy balance and body weight is widely studied in rodents but not in humans. Here we investigated (1) whether the expression of clock genes in human adipose tissue is changed by weight loss and (2) whether these alterations are associated with metabolic parameters.SUBJECTS/METHODS: Subcutaneous adipose tissue (SAT) samples were collected before and after 8 weeks of weight loss on an 800 kcal per day hypocaloric diet (plus 200 g per day vegetables) at the same time of the day. Fifty overweight subjects who lost at least 8% weight after 8 weeks were selected for the study. The expression of 10 clock genes and key metabolic and inflammatory genes in adipose tissue was determined by quantitative real-time PCR.RESULTS: The expression of core clock genes PER2 and NR1D1 was increased after the weight loss. Correlations of PERIOD expression with body mass index (BMI) and serum total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol levels and of NR1D1 expression with total and LDL cholesterol were found that became non-significant after correction for multiple testing. Clock gene expression levels and their weight loss-induced changes tightly correlated with each other and with genes involved in fat metabolism (FASN, CPT1A, LPL, PPARG, PGC1A, ADIPOQ), energy metabolism (SIRT1), autophagy (LC3A, LC3B) and inflammatory response (NFKB1, NFKBIA, NLRP3, EMR1).CONCLUSION: Clock gene expression in human SAT is regulated by body weight changes and associated with BMI, serum cholesterol levels and the expression of metabolic and inflammatory genes. Our data confirm the tight crosstalk between molecular clock and metabolic and inflammatory pathways involved in adapting adipose tissue metabolism to changes of the energy intake in humans.