Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Int J Obes (Lond). 2022 Dec;46(12):2137-2144. doi: 10.1038/s41366-022-01227-8. Epub 2022 Oct 10.
MicroRNAs (miRNAs) represent a class of small non-coding RNAs that regulate gene expression post-transcriptionally and are implicated in the pathogenesis of different diseases. Limited studies have investigated the association of circulating miRNAs with obesity and body fat distribution and their link to obesity-related diseases using population-based data.
We conducted a genome-wide profile of circulating miRNAs in plasma, collected between 2002 and 2005, in 1208 participants from the population-based Rotterdam Study cohort. Obesity and body fat distribution were measured as body mass index (BMI), waist-to-hip ratio (WHR), android-fat to gynoid-fat ratio (AGR), and fat mass index (FMI) measured by anthropometrics and Dual X-ray Absorptiometry. Multivariable linear regression models were used to assess the association of 591 miRNAs well-expressed in plasma with these traits adjusted for potential covariates. We further sought for the association of identified miRNAs with cardiovascular and metabolic diseases in the Rotterdam study and previous publications.
Plasma levels of 65 miRNAs were associated with BMI, 40 miRNAs with WHR, 65 miRNAs with FMI, and 15 miRNAs with AGR surpassing the Bonferroni-corrected P < 8.46 × 10. Of these, 12 miRNAs were significantly associated with all traits, while four miRNAs were associated only with WHR, three miRNAs only with FMI, and miR-378i was associated only with AGR. The most significant association among the overlapping miRNAs was with miR-193a-5p, which was shown to be associated with type 2 diabetes and hepatic steatosis in the Rotterdam Study. Moreover, five of the obesity-associated miRNAs and two of the body fat distribution miRNAs have been correlated previously to cardiovascular disease.
This study indicates that plasma levels of several miRNAs are associated with obesity and body fat distribution which could help to better understand the underlying mechanisms and may have the biomarker potential for obesity-related diseases.
微小 RNA（miRNAs）是一类小的非编码 RNA，通过转录后调控基因表达，参与多种疾病的发病机制。利用基于人群的数据，已有有限的研究调查了循环 miRNA 与肥胖和体脂分布的关联及其与肥胖相关疾病的关系。
我们对 1208 名来自基于人群的鹿特丹研究队列的参与者在 2002 年至 2005 年期间采集的血浆进行了全基因组循环 miRNA 谱分析。肥胖和体脂分布通过人体测量学和双能 X 线吸收法测量的体重指数（BMI）、腰臀比（WHR）、安卓脂肪与女性脂肪比（AGR）和脂肪质量指数（FMI）来衡量。多变量线性回归模型用于评估在调整潜在协变量后，591 种在血浆中表达良好的 miRNA 与这些特征的相关性。我们还在鹿特丹研究和之前的出版物中寻找与心血管和代谢疾病相关的鉴定 miRNA 的关联。
65 种 miRNA 与 BMI 相关，40 种 miRNA 与 WHR 相关，65 种 miRNA 与 FMI 相关，15 种 miRNA 与 AGR 相关，这些都超过了 Bonferroni 校正的 P 值<8.46×10。其中，12 种 miRNA 与所有特征均显著相关，而 4 种 miRNA 仅与 WHR 相关，3 种 miRNA 仅与 FMI 相关，miR-378i 仅与 AGR 相关。重叠 miRNA 中最显著的相关性是 miR-193a-5p，它与鹿特丹研究中的 2 型糖尿病和肝脂肪变性有关。此外，肥胖相关 miRNA 中有 5 种和体脂分布相关 miRNA 中有 2 种之前与心血管疾病相关。
本研究表明，几种 miRNA 的血浆水平与肥胖和体脂分布相关，这有助于更好地理解潜在机制，并可能为肥胖相关疾病提供生物标志物潜力。
