Bile acids regulate lipid metabolism through selective actions on fatty acid absorption

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.

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Publication Details

Journal
Cell Metabolism
Published
2025-12-11
DOI
https://doi.org/10.1016/j.cmet.2025.11.010
Citations
4
Primary Topic
Drug Transport and Resistance Mechanisms
Type
article
Field-Weighted Citation Impact
4.18
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article

Bile acids regulate lipid metabolism through selective actions on fatty acid absorption

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4 citations
Cell Metabolism
Drug Transport and Resistance Mechanisms
4.18
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Bile acids regulate lipid metabolism through selective actions on fatty acid absorption

Alvin P. Chan, Baolong Su, John P. Kennelly, Kelsey E. Jarrett, Elizabeth Smith, Madelaine C. Brearley-Sholto, Thomas Q. de Aguiar Vallim, Heidi M. Schmidt, Andrew Lau, Elizabeth J. Tarling, Michelle E. Steel, Emily Whang, Yajing Gao, Rochelle W. Lai, Kevin J. Williams, Angela Cheng, Anne M Iwata, Gabriella E Rubert, Maria Taveras
article en
4 citations

Abstract

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.

Cell MetabolismVol. 38(2)
University of California, Los Angeles (US), Mattel Children's Hospital (US)
Openalex Percentile: Top 5%
Drug Transport and Resistance Mechanisms
4.18
DOIOpen Access PDFOpenAlex
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