Decreased miR-181a Expression in Monocytes of Obese Patients Is Associated with the Occurrence of Metabolic Syndrome and Coronary Artery Disease

Context: Inflammation during obesity is associated with higher risk of metabolic syndrome and coronary artery disease (CAD). Activation of the inflammatory toll-like receptor (TLR)/nuclear factor kappa B (NF kappa B) signaling in monocytes contributes to inflammation. Weight loss after bariatric surgery leads to significant improvement of obesity-related comorbidities. MicroRNA (miR), a class of small noncoding RNA, have been implicated as negative regulators of inflammatory processes. Objective: This study sought to identify dysregulated miR in monocytes of obese patients associated with TLR/NF kappa B signaling, metabolic syndrome, and CAD. Design, Setting, and Patients: This retrospective study included two independent cohorts of 21 morbidly obese and 125 high-risk obese and nonobese patients in a hospitalized care setting. Intervention: Intervention included bariatric surgery (n = 21) with a 3-month follow-up. Main Outcome Measures: miR expressions in CD14(+) monocytes were determined by microarray analysis. TLR/NF kappa B-related miR were identified by an in silico target prediction analysis. Their expression was validated by quantitative RT-PCR. Their association with metabolic syndrome and angiographically documented CAD was assessed. Results: miR-181a, -181b, and -181d, identified as possible regulators of the TLR/NF kappa B signaling, were decreased in obese monocytes, and weight loss normalized their expression to levels observed in monocytes of lean persons. miR-181a but not miR-181b and miR-181d was associated with a higher number of metabolic syndrome components and with CAD even after adjustment for traditional risk factors, obesity and the metabolic syndrome. Conclusion: This study demonstrates that the TLR/NF kappa B-related miR-181a is down-regulated in monocytes of obese patients and suggests that it is a putative biomarker of metabolic syndrome and CAD. (J Clin Endocrinol Metab 97: E1213-E1218, 2012)