Pivovarova O, Gögebakan Ö, Sucher S, Groth J, Murahovschi V, Kessler K, Osterhoff M, Rudovich N, Kramer A, Pfeiffer A F H
Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany.
Int J Obes (Lond). 2016 Jun;40(6):899-906. doi: 10.1038/ijo.2016.34. Epub 2016 Feb 23.
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.
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).
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.
生物钟协调众多代谢过程，以适应生理反应对昼夜和进食模式的变化，并且其本身也受代谢信号的调节。生物钟在能量平衡和体重调节中的作用在啮齿动物中得到了广泛研究，但在人类中尚未有相关研究。在此，我们调查了：（1）体重减轻是否会改变人类脂肪组织中生物钟基因的表达；（2）这些改变是否与代谢参数相关。
受试者/方法：在每天摄入800千卡低热量饮食（外加每天200克蔬菜）8周前后，于一天中的同一时间采集皮下脂肪组织（SAT）样本。选择50名超重受试者，他们在8周后体重减轻至少8%，纳入本研究。通过定量实时PCR测定脂肪组织中10种生物钟基因以及关键代谢和炎症基因的表达。
体重减轻后，核心生物钟基因PER2和NR1D1的表达增加。发现PERIOD表达与体重指数（BMI）、血清总胆固醇、高密度脂蛋白和低密度脂蛋白（LDL）胆固醇水平之间存在相关性，NR1D1表达与总胆固醇和LDL胆固醇之间存在相关性，经过多重检验校正后这些相关性变得不显著。生物钟基因表达水平及其体重减轻诱导的变化彼此紧密相关，并且与参与脂肪代谢（FASN、CPT1A、LPL、PPARG、PGC1A、ADIPOQ）、能量代谢（SIRT1）、自噬（LC3A、LC3B）和炎症反应（NFKB1、NFKBIA、NLRP3、EMR1）的基因紧密相关。
人类SAT中的生物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生物钟与参与使脂肪组织代谢适应人类能量摄入变化的代谢和炎症途径之间存在紧密的相互作用。
