Circulating miRNAs Detect High vs Low Visceral Adipose Tissue Inflammation in Patients Living With Obesity

脂肪组织 炎症 内科学 胰岛素抵抗 肥胖 接收机工作特性 医学 队列 小RNA 曲线下面积 全身炎症 胃肠病学 肿瘤科 生物信息学 生物 基因 遗传学
作者
Nataly Makarenkov,Yulia Haim,Uri Yoel,Yair Pincu,Tanya Tarnovscki,Idit F. Liberty,Ivan Kukeev,Lior Baraf,Oleg Dukhno,Oleg Zilber,Matthias Blüher,Assaf Rudich,Isana Veksler‐Lublinsky
出处
期刊:The Journal of Clinical Endocrinology and Metabolism [The Endocrine Society]
卷期号:109 (3): 858-867 被引量:2
标识
DOI:10.1210/clinem/dgad550
摘要

Abstract Context The severity of visceral adipose tissue (VAT) inflammation in individuals with obesity is thought to signify obesity subphenotype(s) associated with higher cardiometabolic risk. Yet, this tissue is not accessible for direct sampling in the nonsurgical patient. Objective We hypothesized that circulating miRNAs (circ-miRs) could serve as biomarkers to distinguish human obesity subgroups with high or low extent of VAT inflammation. Methods Discovery and validation cohorts of patients living with obesity undergoing bariatric surgery (n = 35 and 51, respectively) were included. VAT inflammation was classified into low/high based on an expression score derived from the messenger RNA levels of TNFA, IL6, and CCL2 (determined by reverse transcription polymerase chain reaction). Differentially expressed circ-miRs were identified, and their discriminative power to detect low/high VAT inflammation was assessed by receiver operating characteristic–area under the curve (ROC-AUC) analysis. Results Fifty three out of 263 circ-miRs (20%) were associated with high-VAT inflammation according to Mann-Whitney analysis in the discovery cohort. Of those, 12 (12/53 = 23%) were differentially expressed according to Deseq2, and 6 significantly discriminated between high- and low-VAT inflammation with ROC-AUC greater than 0.8. Of the resulting 5 circ-miRs that were differentially abundant in all 3 statistical approaches, 3 were unaffected by hemolysis and validated in an independent cohort. Circ-miRs 181b-5p, 1306-3p, and 3138 combined with homeostatic model assessment of insulin resistance (HOMA-IR) exhibited ROC-AUC of 0.951 (95% CI, 0.865-1) and 0.808 (95% CI, 0.654-0.963) in the discovery and validation cohorts, respectively, providing strong discriminative power between participants with low- vs high-VAT inflammation. Predicted target genes of these miRNAs are enriched in pathways of insulin and inflammatory signaling, circadian entrainment, and cellular senescence. Conclusion Circ-miRs that identify patients with low- vs high-VAT inflammation constitute a putative tool to improve personalized care of patients with obesity.
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