Acute weight loss restores dysregulated circulating micrornas in individuals who are obese

Abstract

Context: Obesity is a global epidemic and an independent risk factor for several diseases. miRNAs are gaining interest as early molecular regulators of various pathological processes. Objective: To examine the miRNA signatures in women who are obese and determine the response of miRNAs to acute weight loss. Methods: Plasma samples were collected from women who are obese (n = 80) before and after acute weight loss (mean, 7.2%). Plasma samples from age-matched lean volunteers (n = 80) were used as controls. Total RNA was extracted from the plasma samples and subjected to NanoString analysis of 822 miRNAs. The expression level of candidate miRNAs was validated in all participants using quantitative real-time PCR analysis. Results: NanoString analysis identified substantial dysregulation of 21 miRNAs in women who are obese that were associated with impaired glucose tolerance, senescence, cardiac hypertrophy, angiogenesis, inflammation, and cell death. Acute weight loss reversed the expression pattern of 18 of these miRNAs toward those seen in the lean control group. Furthermore, real-time PCR validation of all the samples for 13 miRNAs with at least twofold upregulation or downregulation confirmed substantial dysregulation of all the chosen miRNAs in women who are obese at baseline. After acute weight loss, the levels of seven miRNAs in women who are obese and who are lean were comparable, with no statistically significant evidence for differences between the two groups. Conclusions: Our study has provided evidence that the circulating miRNAs associated with various disorders are dysregulated in women who are obese. We also found that seven of these miRNAs showed levels comparable to those in lean controls after acute weight loss in women who are obese.