A Period 2 Genetic Variant Interacts with Plasma SFA to Modify Plasma Lipid Concentrations in Adults with Metabolic Syndrome

García‐Rios, Antonio; Pérez-Martínez, Pablo; Delgado-Lista, Javier; Phillips, Catherine M.; Gjelstad, Ingrid M.F.; Wright, John W.; Karlström, Brita; Kieć‐Wilk, Beata; Hees, Anneke M.J. van; Helal, Olfa; Polus, Anna; Defoort, Catherine; Risérus, Ulf; Blaak, Ellen E.; Lovegrove, Julie A.; Drevon, Christian A.; Roche, Helen M.; López‐Miranda, José

doi:10.3945/jn.111.156968

Cited by 29 publications

(20 citation statements)

References 41 publications

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“…Despite a small number of subjects, our results in the MS group suggest a link between PER2 and REV-ERB ALPHA genes with metabolic syndrome. Indeed, the associations between polymorphisms in the PER2 gene locus may influence lipid metabolism by interacting with total serum fatty acids [38]. One very interesting finding of the present work is the upregulation of the REV-ERB ALPHA gene in all cells fractions over the course of 24 h in VAT and its correlation with BMI and waist circumference.…”

Section: Discussionsupporting

confidence: 50%

Altered Clock Gene Expression in Obese Visceral Adipose Tissue Is Associated with Metabolic Syndrome

et al. 2014

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Clock gene expression was associated with different components of metabolic syndrome (MS) in human adipose tissue. However, no study has been done to compare the expression of clock genes in visceral adipose tissue (VAT) from lean and obese subjects and its clinical implications. Therefore, we studied in lean and obese women the endogenous 24 h expression of clock genes in isolated adipocytes and its association with MS components. VAT was obtained from lean (BMI 21–25 kg/m2; n = 21) and morbidly obese women (BMI >40 kg/m2; n = 28). The 24 h pattern of clock genes was analyzed every 6 hours using RT-PCR. Correlation of clinical data was studied by Spearman analysis. The 24 h pattern of clock genes showed that obesity alters the expression of CLOCK, BMAL1, PER1, CRY2 and REV-ERB ALPHA in adipocytes with changes found in CRY2 and REV-ERB ALPHA throughout the 24 h period. The same results were confirmed in VAT and stromal cells (SC) showing an upregulation of CRY2 and REV-ERB ALPHA from obese women. A positive correlation was observed for REV-ERB ALPHA gene expression with BMI and waist circumference in the obese population. Expression of ROR ALPHA was correlated with HDL levels and CLOCK with LDL. Obese subjects with MS exhibited positive correlation in the PER2 gene with LDL cholesterol, whereas REV-ERB ALPHA was correlated with waist circumference. We identified CRY2 and REV-ERB ALPHA as the clock genes upregulated in obesity during the 24 h period and that REV-ERB ALPHA is an important gene associated with MS.

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Section: Discussionsupporting

confidence: 50%

Altered Clock Gene Expression in Obese Visceral Adipose Tissue Is Associated with Metabolic Syndrome

et al. 2014

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“…These SNPs were located throughout the Per2 gene body and untranslated regions. Another study showed that in patients with metabolic syndrome, SNPs in the Per2 coding region were associated with higher mean plasma serum fatty acids [54]. Thus, Per2 appears to play an integral role in the regulation of ischemic adaptation in the heart and may also contribute to regulation of vascular function and metabolism.…”

Section: Period 2: Potential Role In the Heart Vasculature And In Mmentioning

confidence: 99%

Clock genes in hypertension

Richards

Diaz²,

Gumz

2014

Blood Pressure Monitoring

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The circadian clock plays an integral role in the regulation of physiological processes, including the regulation of blood pressure. However, deregulation of the clock can lead to pathophysiological states including hypertension. Recent work has implicated the circadian clock genes in the regulation of processes in the heart, kidney, vasculature, and the metabolic organs, which are all critical in the regulation of the blood pressure. The goal of this review is to provide an introduction and general overview into the role of circadian clock genes in the regulation of blood pressure with a focus on their deregulation in the etiology of hypertension. This review will focus on the core circadian clock genes CLOCK, BMAL1, Per, and Cry.

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“…83 Among individuals with metabolic syndromes and high levels of saturated fatty acid (SFA),-111G carriers have higher plasma lipid concentrations, 84 suggesting that the -111G/C allele interacts with plasma SFA to modify lipid levels.…”

Section: Per2mentioning

confidence: 99%

Diversity of Human Clock Genotypes and Consequences

Zhang

Ptáček

2013

Progress in Molecular Biology and Translational Science

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The molecular clock consists of a number of genes that form transcriptional and post-transcriptional feedback loops, which function together to generate circadian oscillations that give rise to circadian rhythms of our behavioral and physiological processes. Genetic variations in these clock genes have been shown to be associated with phenotypic effects in a repertoire of biological processes, such as diurnal preference, sleep, metabolism, mood regulation, addiction, and fertility. Consistently, rodent models carrying mutations in clock genes also demonstrate similar phenotypes. Taken together, these studies suggest that human clock-gene variants contribute to the phenotypic differences observed in various behavioral and physiological processes, although to validate this requires further characterization of the molecular consequences of these polymorphisms. Investigating the diversity of human genotypes and the phenotypic effects of these genetic variations shall advance our understanding of the function of the circadian clock and how we can employ the clock to improve our overall health.

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A Period 2 Genetic Variant Interacts with Plasma SFA to Modify Plasma Lipid Concentrations in Adults with Metabolic Syndrome

Cited by 29 publications

References 41 publications

Altered Clock Gene Expression in Obese Visceral Adipose Tissue Is Associated with Metabolic Syndrome

Altered Clock Gene Expression in Obese Visceral Adipose Tissue Is Associated with Metabolic Syndrome

Clock genes in hypertension

Diversity of Human Clock Genotypes and Consequences

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