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Int J Obes (Lond). 2016 Jun;40(6):899-906. doi: 10.1038/ijo.2016.34. Epub 2016 Feb 23.

Regulation of the clock gene expression in human adipose tissue by weight loss.

Author information

1
Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
2
Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany.
3
Department for Radiology and Interventional Therapy, Vivantes Klinikum Neukölln, Berlin, Germany.
4
Laboratory of Chronobiology, Institute for Medical Immunology, Charité University Medicine, Berlin, Germany.

Abstract

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.

PMID:
26902807
DOI:
10.1038/ijo.2016.34
[Indexed for MEDLINE]

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