(P18-33-26) Dietary Fat Shapes Bile Acid-Insulin Coupling in Adults With Obesity

Objectives: Diet shapes the bile acid (BA) pool through host and microbial biotransformation, altering the primary/secondary balance, 12α-hydroxylation, and conjugation patterns. Distinct BA species differentially influence insulin secretion via FXR and TGR5 signaling.

Methods: Twenty-four adults (age = 43.7 ± 11.3 y; BMI = 37.0 ± 6.02 kg/m2) completed a randomized, controlled, crossover, complete feeding trial consisting of three 21-day periods differing only by the addition of whole walnuts, walnut oil, or corn oil. Blood samples were collected during a 6-hour mixed-meal tolerance test at baseline (t0) and every 30 min postprandially (t30-t360). For each bile acid, we fit linear models of baseline-corrected insulin, including treatment, bile acid concentration, and time modeled as a cubic polynomial.

Results: In the corn oil condition, cholic acid (CA; 12α-hydroxylated BA) and deoxycholic acid (DCA; 12α-hydroxylated BA) were positively associated with insulin. These associations were attenuated in the walnut treatments, including the walnut x CA interaction (β = -0.49; p < 0.001) and the DCA x Treatment interactions for both walnuts (β = -0.16; p < 0.01) and walnut oil (β = -0.22; p < 0.01). Taurodeoxycholic acid showed significant BA x Time interactions. Glycolithocholic acid (GLCA) was treatment-invariant; higher GLCA was associated with lower insulin (β = -0.73; p < 0.01). When BA x Treatment terms were not significant, both walnut and walnut oil lowered insulin relative to corn oil (β = -19.9; p < 0.01; β = -17.65; p < 0.02). Exploratory mediation analyses did not identify statistically significant indirect effects of treatment on insulin.

Conclusions: These findings indicate that walnuts and walnut oil attenuate bile acid-insulin coupling in a bile acid-specific manner, with the strongest effects observed for 12α-hydroxylated bile acids such as CA and DCA. The consistent Treatment x Bile Acid interactions suggest that walnuts modify bile acid-insulin coupling (moderation) rather than acting primarily on insulin through shifts in bile acid concentrations. Future analyses will integrate BA profiles with microbiome data to identify microbial drivers of diet-microbiome-host interactions.

Funding Sources: USDA NIFA & Personalized Nutrition Initiative External Partners Program