Changes in Circulating miR-375-3p and Improvements in Visceral and Hepatic Fat Contents in Response to Lifestyle Interventions: The CENTRAL Trial

OBJECTIVE To investigate whether changes in circulating levels of pancreatic islet–related miRNA-375 (miR-375) are related to improved visceral and intrahepatic fat accumulation. RESEARCH DESIGN AND METHODS This study included adults with abdominal obesity from an 18-month weight loss lifestyle intervention trial. Circulating miR-375-3p was measured at baseline and 18 months. MRI was performed (n = 139) to assess 18-month changes in abdominal and intrahepatic fat depots. RESULTS Circulating miR-375-3p was related to fasting insulin and insulin resistance in participants with prediabetes. After the interventions, there was a significant increase of miR-375-3p (P < 0.001). Greater increase in miR-375-3p was associated with greater reductions of visceral (P = 0.024) and deep subcutaneous (P < 0.001) adipose tissues and intrahepatic fat content (P = 0.012). CONCLUSIONS Increases in circulating miR-375-3p were associated with visceral and intrahepatic fat reduction. Changes in circulating pancreatic islet–related miR-375-3p may be linked to improved diabetogenic fat depots during weight loss lifestyle interventions.