Changes in circulating microRNAs-99/100 and reductions of visceral and ectopic fat depots in response to lifestyle interventions: the CENTRAL trial

Abstract

MicroRNAs (miRNAs) are short noncoding RNAs and important posttranscriptional regulators of gene expression. Adipose tissue is a major source of circulating miRNAs; adipose-related circulating miRNAs may regulate body fat distribution and glucose metabolism. We investigated how changes in adipose-related circulating microRNAs-99/100 (miR-99/100) in response to lifestyle interventions were associated with improved body fat distribution and reductions of diabetogenic ectopic fat depots among adults with abdominal obesity. This study included adults with abdominal obesity from an 18-mo diet and physical activity intervention trial. Circulating miR-99a-5p, miR-99b-5p, and miR-100-5p were measured at baseline and 18 mo; changes in these miRNAs in response to the interventions were evaluated. The primary outcomes were changes in abdominal adipose tissue [visceral (VAT), deep subcutaneous (DSAT), and superficial subcutaneous (SSAT) adipose tissue; cm2] (n=144). The secondary outcomes were changes in ectopic fat accumulation in the liver (n=141) and pancreas (n=143). Greater decreases in miR-100-5p were associated with more reductions of VAT (β±SE per 1-SD decrease: -9.63±3.13 cm2; P=0.0025), DSAT (β±SE: -5.48±2.36 cm2; P=0.0218), SSAT (β±SE: -4.64±1.68 cm2; P=0.0067), and intrahepatic fat percentage (β±SE: -1.54%±0.49%; P=0.0023) after the interventions. Similarly, participants with greater decrease in miR-99a-5p had larger 18-mo reductions of VAT (β±SE: -10.12±3.31 cm2 per 1-SD decrease; P=0.0027) and intrahepatic fat percentage (β±SE: -1.28%±0.52%; P=0.015). Further, decreases in circulating miR-99b-5p (β±SE: per 1-SD decrease: -0.44%±0.21%; P=0.038) and miR-100-5p (β±SE: -0.50%±0.23%; P=0.033) were associated with a decrease in pancreatic fat percentage, as well as improved glucose metabolism and insulin secretion at 18 mo. Decreases in circulating miR-99-5p/100-5p expression induced by lifestyle interventions were related to improved body fat distribution and ectopic fat accumulation. Our study suggests that changes in circulating adipose-related miR-99-5p/100-5p may be linked to reducing diabetogenic fat depots in patients with abdominal obesity.This trial was registered at clinicaltrials.gov as NCT01530724.