MON-250 Bile Acids: Potential Links to Overweight/Obesity and Androgen Levels in Pubertal Girls

Abstract Disclosure: S.I. Malave: None. N.D. Shaw: None. S. Molsberry: None. S. Denslow: None. F.B. Lih: None. Background: Pubertal girls with higher body mass index (BMI) or total body fat (TBF) have higher androgen levels. We previously conducted an untargeted metabolomics study in a longitudinal cohort of healthy pubertal girls who were pre-menarchal at baseline to investigate this association. We demonstrated that several bile acids (BAs) were associated with BMI, TBF and serum androstenedione (AD). Methods: To further investigate these relationships, a panel of 18 BAs (including primary, secondary, conjugated, and unconjugated forms) was measured using liquid chromatography mass spectrometry (LCMS). Blood samples (n=215) were collected from participants at up to 8 study visits that also included Tanner staging, breast ultrasound, and DXA to calculate TBF. Serum total testosterone (TT), free testosterone (FT), AD, and dehydroepiandrosterone sulfate (DHEAS) were measured by LCMS. Bile acid and hormone values were natural log transformed and standardized; body composition variables were analyzed as BMI z-scores and TBF percent, respectively. Associations between TBF or BMI, hormone level, and BAs were examined using generalized estimating equation models with the exposure lagged by one study visit. Models were adjusted for time since baseline visit, age at baseline, menarche status, race (White vs non-White), and breast morphological stage. Benjamini-Hochberg false discovery rate (FDR) adjusted P-values were calculated to account for multiple testing.Results: 82 participants (aged 10.9 ± 1.4 SD years at baseline; 55% White, 29% Black, 16% Other; 65% normal weight, 35% overweight/obese) contributed an average of 2.62 blood samples over 1.20 years of follow-up. BAs levels varied within participant over time (intraclass correlation coefficients [ICCs] ≤0.5) and were not associated with menarchal status. BMI and TBF were significantly negatively associated with total BAs (BMI: β= -0.34 (95% confidence interval (CI): -0.51, -0.17), pFDR=0.001; TBF: β=-0.06 (95% CI: -0.09, -0.04), pFDR =0.0001) as well as with 11 individual BA species. FT was nominally positively associated with two primary, conjugated BAs: taurocholic acid (β=0.45 (95% CI: 0.01, 0.89), pFDR =0.21) and taurodeoxycholic acid (β=0.77 (95% CI: 0.05, 1.49), pFDR =0.17). Conclusion: While alterations in BA synthesis and transport have been reported among adults with obesity and insulin resistance, this is the first study to demonstrate a negative association between BMI (or TBF) and BAs in healthy girls across a spectrum of body weights. We also observed a positive association between two BAs and FT that warrants further exploration. Together, these results suggest biological links between altered BA signaling, overweight/obesity, and androgen production among pubertal girls. Presentation: Monday, July 14, 2025