Circulating MIR148A associates with sensitivity to adiponectin levels in human metabolic surgery for weight loss

摘要

Objective We sought to discover secreted biomarkers to monitor the recovery of physiological adiponectin levels with metabolic surgery, focusing on epigenetic changes that might predict adiponectin function. Design We conducted a prospective observational study of patients undergoing metabolic surgery by Roux-en-Y Gastric Bypass (RYGB) for weight loss in a single center (IRB GHS # 1207-27). Methods All patients ( n ?=?33; 27 females; 6 males) signed informed consent. Metabolites, adiponectin and MIR148A were measured in fasting plasma. We followed MIQE for transcript profiles. Results Patients lost on average 47?±?12% excess BMI (%EBMI) after 12 weeks. Adiponectin pre, post or delta (post minus pre) did not correlate with %EBMIL. A decrease in adiponectin following weight loss surgery was observed in a subset of patients, chi-square test of independence rejects the null hypotheses that the liver DNA methyltransferase 1 (DNMT1) and delta adiponectin are independent ( chi-square statistics χ ~(2) ?=? 6.9205 , P ?=? 0.00852 , n ?=? 33 ), as well as MIR148A and delta adiponectin are independent ( chi-square statistics χ ~(2) ?=? 9.6823 , P ?=? 0.00186 , n ?=? 33 ). The presence of plasma MIR148A allows identification of patients that appear to be adiponectin insensitive at baseline. Conclusion We combined the presence of plasma MIR148A, the concentration of total adiponectin and the expression of DNA methyltransferase 1 (DNMT1) in liver biopsy tissue to identify patients with non-physiological adiponectin. Weight loss and physical activity interventions complemented with the new method presented here could serve to monitor the physiological levels of adiponectin, thought to be important for long-term weight loss maintenance.