Clock genes are implicated in the human metabolic syndrome

Abstract

Background: Clock genes play a role in adipose tissue (AT) in animal experimental models. However, it remains to be elucidated whether these genes are expressed in human AT. Objective: We investigated the expression of several clock genes, Bmal1, Per2 and Cry1, in human AT from visceral and subcutaneous abdominal depots. A second objective was to elucidate whether these clock genes expressions were related to the metabolic syndrome features. Methods: Visceral and subcutaneous AT samples were obtained from morbid obese men (n ¼ 8), age: 42713 years and body mass indexX40 kg/m 2 , undergoing laparoscopic surgery due to obesity. Biopsies were taken as paired samples at the beginning of the surgical process (1100 hour). Metabolic syndrome features such as waist circumference, plasma glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein (LDL) cholesterol were also studied. Homeostasis model assessment index of insulin resistance was also calculated. The expression of the different clock genes, hBmal1, hPer2 and hCry1, was determined by quantitative real-time PCR. Results: Clock genes were expressed in both human AT depots. hBmal1 expression was significantly lower than hPer2 and hCry1 in both AT (Po0.001). All genes were highly correlated to one another in the subcutaneous fat, while no correlation was found between Bmal1 and Per2 in the visceral AT. Clock genes AT expression was associated with the metabolic syndrome parameters: hPer2 expression level from visceral depot was inversely correlated to waist circumference (Po0.01), while the three clock genes studied were significantly and negatively correlated to total cholesterol and LDL cholesterol (Po0.01). Conclusion: We have demonstrated for the first time in humans that clock genes are expressed in both subcutaneous and visceral fat. Their association with abdominal fat content and cardiovascular risk factors may be an indicator of the potential role of these clock genes in the metabolic syndrome disturbances.

Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man

“…[40][41][42][43][44][45] It has also recently been reported that the expression of several components of the molecular clock (Per2,Cry1, Bmal1) in adipose tissue are associated with features of the metabolic syndrome in man. 46 …”

Abnormal expressions of circadian-clock and circadian clock-controlled genes in the livers and kidneys of long-term, high-fat-diet-treated mice

“…20,21,26,[31][32][33] Circadian-clock genes are associated with the pathophysiology Diet-induced obesity on circadian-clock systems M-C Hsieh et al of metabolic syndrome due to impairment of adipogenesis by a deficiency in Bmal1. 34 Deletion of Bmal1 also induces arrhythmicity, early onset of age-related pathologies, including myopathy and arthropathy, and altered hepatic carbohydrate metabolism; 20,35,36 Clock-mutant mice are hyperphagic and obese, and similarly develop metabolic syndrome.…”

Obesity and shift work: chronobiological aspects

“…The reason may be the fact that components such as the wake-sleep cycle, thermogenesis, food intake, and lipid and glucose metabolism are under circadian regulation. This regulation synchronises available and expenditure energy to external changes in the environment, such as the light -dark phase (15) . Such rhythms are coordinated by circadian clocks which are intrinsically maintained by molecular mechanisms whose objective is to condition humans to adapt to environmental changes.…”