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Obesity and associated comorbidities—insulin resistance, diabetes, dyslipidemia, and cardiovascular diseases—are rooted in myriad metabolic dysfunctions orchestrated in part by microRNAs. This chapter focuses on the most frequently reported microRNAs differentially expressed in human obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. The roles of miR-122, miR-126, miR-146a, miR-155, miR-21, miR-223, miR-27a, miR-29a, miR-34a, and miR-375 in human metabolic disease are examined with a focus on T2DM in humans and potential mechanisms of action. Finally, the use of these miRNAs as biomarkers of metabolic disease and as measures of the clinical efficacy of therapeutics is discussed.

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