SIRT1and SIRT7expression in adipose tissues of obese and normal-weight individuals is regulated by microRNAs but not by methylation status

Autor: Kurylowicz, A, Owczarz, M, Polosak, J, Jonas, M I, Lisik, W, Jonas, M, Chmura, A, Puzianowska-Kuznicka, M
Zdroj: International Journal of Obesity (formerly International Journal of Obesity and Related Metabolic Disorders); November 2016, Vol. 40 Issue: 11 p1635-1642, 8p
Abstrakt: Background/Objective:: Given their importance in the regulation of metabolism, sirtuins (SIRTs) constitute promising subjects of research on the pathogenesis of obesity and the metabolic syndrome. The aim of this study was to assess whether obesity in humans is associated with changes in the expression of SIRTgenes in adipose tissue and whether epigenetic mechanisms, DNA methylation and microRNA (miRNA) interference, mediate in this phenomenon. Subjects/Methods:: The expression of SIRTsand of SIRT1and SIRT7mRNA-interacting miRNAs was evaluated by real-time PCR in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of 58 obese (body mass index (BMI) >40?kg?m-2) and 31 normal-weight (BMI 20–24.9?kg?m-2) individuals. The methylation status of SIRTswas studied by the methylation-sensitive digestion/real-time PCR method. Results:: SIRT1mRNA levels were lower in adipose tissues of obese patients than of normal-weight controls (VAT: P=0.0002, SAT: P=0.008). In contrast, expression of SIRT7was higher in adipose tissues of obese patients than in the control group (VAT: P=0.001, SAT: P=0.008). The mean methylation of the SIRT1and SIRT7CpG islands was similar in tissues with high and low expression of these genes, and there was no correlation between the level of expression and the level of methylation. On the other hand, expression of SIRT1in VAT of obese subjects correlated negatively with the expression of miR-22-3p (P<0.0001, rs=-0.514), miR-34a-5p (P=0.01, rs=-0.326) and miR-181a-3p (P<0.0001, rs=-0.536). In turn, expression of SIRT7in VAT of slim individuals correlated negatively with the expression of miR-125a-5p (P=0.003, rs=-0.562) and miR-125b-5p (P=0.018, rs=-0.460). Conclusions:: We observed obesity-associated downregulation of SIRT1and upregulation of SIRT7mRNA levels that were not associated with the methylation status of their promoters. We found a negative correlation between mRNA levels of SIRT1in VAT of obese individuals and SIRT7in VAT of the normal-weight subjects and expression of the relevant miRNAs.
Databáze: Supplemental Index
Externí odkaz: