Circulating Levels of microRNA-122 and Hepatic Fat Change in Response to Weight-Loss Interventions: CENTRAL Trial

Abstract

Purpose: Little is known about the relations between changes in circulating microRNA-122 (miR-122) and liver fat in response to weight-loss interventions. We aimed to investigate the association between 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 diet or a Mediterranean/low-carbohydrate diet. After 6 months of dietary intervention, each diet group was further randomized into added physical activity groups or no added physical activity groups for the following 12 months of intervention. The current study included 220 participants at baseline and 134 participants with repeated measurements on serum miR-122 and hepatic fat content over 18 months.

Results: Serum miR-122 significantly increased from baseline to 18 months, while no difference was observed across the 4 intervention groups. We found a significant association between miR-122 and hepatic fat content at baseline, as per unit increment in log-transformed miR-122 was associated with 3.79 higher hepatic fat content (P < 0.001). Furthermore, we found that higher elevations in miR-122 were associated with less reductions in hepatic fat percentage during 18-month interventions (β = 1.56, P = 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).

Conclusions: Our data indicate that participants with higher elevation in serum miR-122 may benefit less in reduction of hepatic fat content in response to diet and physical activity interventions.

Keywords: hepatic fat; microRNA-122; randomized controlled trial; weight-loss interventions.

Figure 1.

Log transformed microRNA-122 (miR-122) levels between different dietary intervention groups. Values were expressed as adjusted least square means ± SE for miR-122 levels at baseline and changes between 18 months and baseline. (A) Adjusted for age, sex, and abdominal obesity status. (B) Adjusted for age, sex, concurrent weight change percentage, physical activity intervention groups, and baseline miR-122 levels. The number of participants was 70 for low-fat group and 64 for Mediterranean/low-carbohydrate group at both baseline and 18 months.

Figure 2.

Association between changes in liver fat content and log-transformed microRNA-122 (miR-122) levels between 18 months and baseline, stratified by baseline risk factors. Adjusted for age, sex, intervention groups, concurrent weight change percentage, concurrent physical activity change, concurrent serum high-density lipoprotein cholesterol change, concurrent serum triglycerides change, concurrent fasting glucose levels change, baseline miR-122 levels, and baseline liver fat content.