(P18-014-25) Pinto Bean Consumption Enhances Bile Acid Metabolism and Gut-Liver Axis Function in Estrogen-Deficient Mice

Objectives: This study assessed the effects of pinto bean (PB) supplementation on glucose and lipid homeostasis, bile acid metabolism, and gut-liver axis function of estrogen-deficient mice.

Methods: Estrogen deficiency was induced in 3-mo-old female C57BL/6 mice by ip injection of either vinyl cyclohexene diepoxide (VCD, 160 mg/kg in sesame oil) or vehicle for 30 d. Estrogen deficiency was confirmed by vaginal smear cytology and serum follicle-stimulating hormone (FSH). Mice were then randomly assigned to four groups (n=15/group) based on estrogen status (VCD or vehicle) and diet [control (AIN-93M) or 10% (wt/wt) PB] for 16 wks. Fasting blood glucose (FBG), glucose tolerance tests (GTT), and serum total cholesterol, aspartate transaminase (AST), and alanine transaminase (ALT) were assessed. Bile acid metabolites were analyzed by LC-MS/MS. RNA sequencing and qPCR were used to examine gene expression related to hepatic bile acid metabolism (Fgfr4, Cyp7a1, Fxr, Klb) and lipid homeostasis (Ldlr) and jejunal lipid and bile acid metabolism (Pparg, Nr1h4) markers. Data were analyzed using a 2-way ANOVA, followed by post hoc tests when p< 0.05.

Results: VCD increased FBG but had no effect on GTT; however, PB had no effect on FBG but tended (p = 0.063) to promote glucose tolerance. PB reduced (p = 0.021) serum total cholesterol in the vehicle group but not in the VCD group. PB tended (p = 0.093) to reduce serum liver function marker AST in the VCD group but had no effect on ALT. PB significantly increased serum bile acid metabolites 7-keto deoxycholic acid, alpha-muricholic acid, and cholic acid levels, and decreased taurodeoxycholic acid in both groups. RNA sequencing showed that VCD induced differential gene expression in control-fed mice, whereas PB had no major impact. Similarly, PB had no significant effect on hepatic gene expression of bile acid receptors (Cyp7a1, Fgfr4, Fxr) but increased (p = 0.043) Klb expression in estrogen-deficient mice. PB increased jejunal Nr1h4 and reduced hepatic Ldlr gene expression in both groups.

Conclusions: PB supplementation modulated bile acid metabolism and gut-liver axis function but had a modest effect on glucose tolerance, suggesting potential benefits for metabolic health in estrogen-deficiency.

Funding Sources: NIH-NIA/NICCH (R15AT011962), B. Pass Scholarship, and Williams Professorship.