Abstract 8879: Circulating Levels of MicroRNA-122 and Hepatic Fat Changes in Response to Lifestyle Intervention: Central Magnetic Resonance Imaging Randomized Controlled Trial

Abstract

Introduction: Compelling evidence has linked liver-specific microRNA-122 (miR-122) expression with hepatic fat distribution; however, little is known about the relations between changes in circulating miR-122 and liver fat in response to weight-loss interventions. We aimed to prospectively investigate the association between serum miR-122 and changes of hepatic fat content during 18-month diet and physical activity interventions. Methods: The CENTRAL trial is an 18-month randomized controlled trial among adults with abdominal obesity or dyslipidemia. Subjects were randomly assigned to a low-fat (LF) diet or a Mediterranean/low-carbohydrate (MED/LC) diet. After six months of dietary intervention, each diet group was further randomized into added physical activity groups (LFPA+, MED/LCPA+) or no added physical activity groups (LFPA-, MED/LCPA-) for the following 12 months of intervention. The current study included 220 participants with repeated measurements on serum miR-122 and hepatic fat content (percentage) over 18 months. Results: In the study participants, serum concentration of miR-122 significantly increased from baseline to 18 months, while no difference was observed across the four intervention groups. We found a significant association between miR-122 and hepatic fat percentage at baseline, as per unit increment in log-transformed miR-122 was associated with 3.79 higher hepatic fat content ( P trend<0.001). In addition, we found that a higher elevation in log-transformed miR-122 was associated with a greater reduction in hepatic fat percentage during 18-month interventions, independent of weight loss (β=1.56, P trend=0.002). We also found a significant interaction between changes in miR-122 and baseline fasting plasma glucose with hepatic fat content changes in 18 months ( P interaction=0.02). The association between changes in miR-122 and hepatic fat content changes appeared to be stronger among participants with higher baseline fasting glucose levels than those with lower levels. Conclusion: Our data indicate that participants with higher serum miR-122 levels may benefit more in reduction of hepatic fat content in response to Mediterranean/low-carbohydrate diet and physical activity interventions.