Differential miRNA Expression in Omental Adipose Tissue and in the Circulation of Obese Patients Identifies Novel Metabolic Biomarkers

Abstract

BACKGROUND: Omental fat accumulation is associated with development of the metabolic syndrome, although its molecular characteristics are poorly understood. Mi(cro)RNAs (miRNAs), a class of small noncoding RNAs, are known to regulate various metabolic processes, although their role in obesity and the metabolic syndrome is not clearly defined. This study sought to characterize the miRNA expression in omentum, sc fat and in the circulation of obese and nonobese individuals. Their potential as noninvasive metabolic biomarkers was also explored. METHODS: miRNA was extracted from paired omentum and sc fat tissues, and blood samples, from a total of 50 obese and nonobese patients. A miRNA microarray was performed and a panel of differentially expressed miRNAs validated using RQ-PCR. RESULTS: The miRNA expression profiles were unique for omentum and paired sc fat; no correlation in miRNA expression was observed between these two fat depots. Expression of two miRNAs (miR-17-5p and miR-132) differed significantly between obese and nonobese omental fat (P = 0.048 and P = 0.016). This expression pattern was reflected in the circulation in which these same two miRNAs were also significantly dysregulated in blood from obese subjects. The miRNA expression in omental fat and blood from obese patients correlated significantly with body mass index, fasting blood glucose, and glycosylated hemoglobin. CONCLUSION: This study demonstrates that candidate metabolic miRNAs are altered in adipose tissue and circulation of the obese. Omental fat tissue and systemic miRNA levels reflect components of the metabolic syndrome, highlighting their potential as novel biomarkers for this complex syndrome.