Bile acids (BAs) are synthesized from cholesterol in the liver and are essential for nutrient absorption. The host-derived primary BAs are transformed into secondary BAs in the intestine. Various BA subtypes may play pivotal roles as endocrine molecules to affect glucose and insulin metabolism. We tested whether changes in distinct BA subtypes were associated with improved glucose and insulin metabolism among adults with overweight and obesity who participated in a weight-loss diet intervention trial. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 months after the intervention; 6-month changes in BAs were calculated (n=515) . When we analyzed associations of BA changes with changes in fasting glucose, insulin, and insulin resistance at 6 months, more decreases in several primary BAs (CDCA, taurocholate [TCA], and taurochenodeoxycholate [TCDCA]) and secondary TDCA were associated with larger reductions of glucose (PFDR <0.for all) , although the associations were dependent on concurrent weight changes. The decreases in primary BAs (including CA, CDCA, TCA, TCDCA) and secondary BAs (including DCA, GDCA, TDCA, GUDCA) were significantly related to improved hyperinsulinemia and insulin resistance, independent of weight changes. Also, we found significant interactions between dietary fat intake and changes in lithocholate and glycolithocholate for changes in insulin metabolism. Further, the initial changes in several primary and secondary BAs showed significant associations for 2-year improvements in glucose/insulin metabolism.

In conclusion, decreases in distinct primary and secondary BAs during weight-loss dietary interventions were associated with improved glucose and insulin metabolism. Changes in various BA subtypes were related to the improved insulin metabolism independent of weight loss status during the interventions.


Y.Heianza: None. X.Wang: None. H.Ma: None. J.Rood: None. C.B.Clish: None. G.Bray: None. F.Sacks: None. L.Qi: None.


National Institutes of Health (DK091718, DK100383, DK115679)

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at