Abstract P119: Circulating microRNA-122 and Improvement in Cardiovascular Health in Response to Weight-Loss Diets: The Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) Trial

Introduction: The microRNA-122 (miR-122) is widely involved in the post-transcriptional regulation of glucose and lipid metabolism, and cardiovascular system. Hypothesis: We assessed the hypothesis that decrease in circulating miR-122-5p would be associated with the improvement in cardiovascular health (CVH) score and each component health metric in response to dietary weight-loss interventions. Methods: Circulating miR-122-5p levels were measured at baseline and 6 months among 509 participants with overweight or obesity from the POUNDS LOST trial. We evaluated the CVH score using the newly updated algorithm -life’s essential 8 and calculated the composite score from the available biological health factors (body mass index [BMI], blood lipids, blood glucose, and blood pressure) across the 2-year intervention period. Results: At baseline, lower levels of miR-122-5p were associated with higher CVH scores (P<0.001). Greater decreases in log-transformed miR-122-5p induced by calorie-restricted diets were significantly associated with greater improvement in overall CVH score (β[SE]= -2.98[0.7], P<0.001), non-HDL metric (β[SE]= -3.72[1.33], P=0.005) and BMI metric (β[SE]= -4.78[1.12], P<0.001) over 6 months. The trajectory of the composite CVH score over the 2-year intervention period differed significantly between the patterns of change in miR-122-5p ( P time*miR-122-5p =0.001). We also found a significant interaction between change in miR-122-5p and dietary fat intake on the 6-months change in CVH ( P = 0.025); a greater decrease in miR-122-5p showed a greater improvement in CVH at 6 months among participants assigned to a low-fat diet. Conclusions: In conclusion, participants with decreased circulating miR-122-5p levels in response to dietary weight-loss interventions had significant improvement in CVH and achieved CVH benefits most strongly when consuming a low-fat diet.