Bile acids are formed in the liver from cholesterol and perform critical functions in nutrition absorption and metabolic control. Dyslipidemia is associated with altered bile acid metabolism, and microRNA-34a (miR-34a) may play a critical role in the therapy of lipid homeostasis by regulating bile acid production. The study comprised 520 patients in a weight-loss dietary intervention (the POUNDS Lost trial) who had data on bile acids and miR-34a. MiR-34a and bile acid subtypes (primary and secondary unconjugated bile acids, as well as taurine-/glycine-conjugates) were evaluated in the blood at baseline and 6 months after the intervention. Improvements in lipids (triglycerides and cholesterol) as a result of the therapies were measured as outcomes.
Greater levels of main bile acids (chenodeoxycholate (CDCA), glycocholate (GCA), taurocholate (TCA), and glycochenodeoxycholate (GCDCA) at baseline were related to higher triglyceride levels (PFDR<0.05). Greater reductions in the principal bile acid subtypes (CDCA, GCA, TCA, GCDCA, and taurochenodeoxycholate [TCDCA]) in response to the therapies were significantly linked with higher triglyceride reductions at 6 months (PFDR<0.05 for all). Decreases in secondary bile acids (deoxycholate and its conjugated derivatives) were also associated with lower triglycerides. Similarly, reductions in total cholesterol after 6 months were related to reductions in main (GCA, GCDCA, TCDCA) and secondary bile acid subtypes. Researchers discovered that higher levels of miR-34a at baseline were associated with higher levels of triglycerides (P=0.038) and primary bile acids (such as CA, CDCA, GCA, and TCA [PFDR<0.05 for all]), but not with secondary bile acids. Furthermore, alterations in miR-34a caused by a weight-loss diet were positively linked with changes in the principal bile acid subtypes (CDCA, GCA, and GCDCA). Changes in particular main and secondary bile acid subtypes were linked to lipid profile improvements in response to weight-loss diet programs. Circulating miR-34a may contribute to changes in main bile acid subtypes in obese persons.