Abstract 048: Changes In Bile Acid Metabolism, Circulating MicroRNA-34a, And Improvements In Lipid Profiles In Response To Weight-loss Diets: The Pounds Lost Trial

Background: Bile acids are synthesized from cholesterol in the liver and play pivotal roles in nutrient absorption and metabolic regulation. Altered bile acid metabolism is related to dyslipidemia, and microRNA-34a (miR-34a) may play a pivotal role in the treatment of lipid homeostasis by regulating the bile acid biosynthesis. Hypothesis: We investigated whether weight-loss diet-induced changes in primary and secondary bile acids were associated with the improvements in lipid profiles. We also tested the role of circulating miR-34a in the altered bile acid metabolism in adults with overweight and obesity. Methods: A total of 520 participants of a weight-loss dietary intervention (the POUNDS Lost trial) with data on bile acids and miR-34a were included in the present analysis. Circulating levels of miR-34a and bile acid subtypes (primary and secondary unconjugated bile acids and their taurine-/glycine-conjugates) were measured at baseline and 6 months after the intervention. Outcome measurements were improvements in lipids (triglycerides and cholesterol) in response to the interventions. Results: At baseline, higher levels of primary bile acids (chenodeoxycholate (CDCA), glycocholate (GCA), taurocholate (TCA), and glycochenodeoxycholate (GCDCA) were associated with elevated levels of triglycerides ( P FDR <0.05). Greater decreases in the primary bile acid subtypes (CDCA, GCA, TCA, GCDCA, and taurochenodeoxycholate [TCDCA]) in response to the interventions were significantly associated with larger reductions of triglycerides at 6 months ( P FDR <0.05 for all). Decreases in secondary bile acids (deoxycholate and its conjugated forms) also showed significant associations with decreases in triglycerides. Similarly, reductions of total cholesterol at 6 months were associated with decreases in the primary (such as GCA, GCDCA, TCDCA) and secondary bile acid subtypes. We found that greater levels of miR-34a at baseline were related to higher levels of triglycerides at baseline (p=0.038) and higher levels of primary bile acids (such as CA, CDCA, GCA, and TCA [PFDR <0.05 for all]) but not with the secondary bile acids at baseline. Further, weight-loss diet-induced changes in miR-34a were positively correlated with changes in the primary bile acid subtypes (CDCA, GCA, and GCDCA). Conclusions: Changes in the specific primary and secondary bile acid subtypes were related to the improvements in lipid profiles in response to weight-loss diet interventions. Circulating miR-34a might in part contribute to the alterations in the primary bile acid subtypes in obese adults.