2025/12/11 by Alvin P. Chan, Kelsey E. Jarrett, Rochelle W. Lai +16 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Drug Transport and Resistance Mechanisms #Gut microbiota and health #Liver Disease Diagnosis and Treatment
paper · doi:10.1016/j.cmet.2025.11.010
openalex created_date 2025/12/11 · openalex publication_date 2025/12/11 · openalex updated_date 2026/07/30
Intestinal lipid absorption, the entry point for fats into the body, requires the coordinated actions of bile acids and lipases. Here, we uncover distinct yet cooperative roles of bile acids in driving the differential uptake of dietary fatty acids. We first decreased the bile acid pool size by disrupting the rate-limiting enzyme in bile acid synthesis, Cyp7a1, using liver-directed gene editing in mice. Compared with lipase inhibition, reduced bile acids prevented diet-induced obesity, increased anorectic hormones, suppressed excessive eating, and improved systemic lipid metabolism. Remarkably, decreasing bile acids selectively reduced the absorption of saturated fatty acids but preserved polyunsaturated fatty acids. By targeting additional bile acid enzymes, we identified specific functions of individual bile acid species. Mechanistically, we show that cholic acid preferentially solubilizes polyunsaturated fatty acids into mixed micelles for intestinal uptake. Our studies demonstrate that bile acids can selectively control fatty acid uptake, revealing insights for future interventions in metabolic diseases.