Elevated and Correlated Expressions of miR-24, miR-30d, miR-146a, and SFRP-4 in Human Abdominal Adipose Tissue Play a Role in Adiposity and Insulin Resistance

OBJECTIVE: We explored the relationships among microRNAs (miRNAs) and SFRP4, as they relate to adipose tissue functions including lipolysis, glucose and glycerol turnover, and insulin sensitivity. METHODS: Abdominal adipose tissue (AbdAT) levels of thirteen microRNAs (miRNAs), SFRP4, and VEGF in lean nondiabetic subjects (n = 7), subjects with obesity (n = 5), and subjects with obesity and type 2 diabetes (T2DM) (n = 5) were measured by qPCR. Insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp. Osmium fixation and Coulter counting were used for adipocyte sizing. Data were analyzed using generalized linear models that adjusted for age, gender, and ethnicity. RESULTS: AbdAT miR-24, miR-30d, and miR-146a were elevated in subjects with obesity (P < 0.05) and T2DM (P < 0.1) and positively correlated with measures of percent body fat by DXA (r(miR.24) = 0.894, r(miR.146a) = 0.883, P < 0.05), and AbdAT SFRP4 (r(miR.30) = 0.93, r(miR.146a) = 0.88, P < 0.05). These three miRNAs additionally correlated among themselves (r(miR.24~miR.146a) = 0.90, r(miR.30~miR.146a) = 0.85, P < 0.01). CONCLUSIONS: This study suggests a novel association between the elevated levels of miRNAs miR-24, miR-30d, and miR-146a (apparently coregulated) and the level of SFRP4 transcript in AbdAT of subjects with obesity and T2DM. These molecules might be part of a regulatory loop involved in AbdAT remodeling/adiposity and systemic insulin resistance. This trial is registered with NCT00704197.