Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice
Open accessAbstract
Activation of farnesoid X receptor (FXR) markedly attenuates development of atherosclerosis in animal models. However, the underlying mechanism is not well elucidated. Here, we show that the FXR agonist, obeticholic acid (OCA), increases fecal cholesterol excretion and macrophage reverse cholesterol transport (RCT) dependent on activation of hepatic FXR. OCA does not increase biliary cholesterol secretion, but inhibits intestinal cholesterol absorption. OCA markedly inhibits hepatic cholesterol 7α‐hydroxylase ( Cyp7a1 ) and sterol 12α‐hydroxylase ( Cyp8b1 ) partly through inducing small heterodimer partner, leading to reduced bile acid pool size and altered bile acid composition, with the α/β‐muricholic acid proportion in bile increased by 2.6‐fold and taurocholic acid (TCA) level reduced by 71%. Overexpression of Cyp8b1 or concurrent overexpression of Cyp7a1 and Cyp8b1 normalizes TCA level, bile acid composition, and intestinal cholesterol absorption. Conclusion : Activation of FXR inhibits intestinal cholesterol absorption by modulation of bile acid pool size and composition, thus leading to increased RCT. Targeting hepatic FXR and/or bile acids may be useful for boosting RCT and preventing the development of atherosclerosis. (H epatology 2016;64:1072‐1085)
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FXR knockout mice demonstrated better recovery following myocardial infarction through reduced apoptosis and fibrosis.
“Moreover, FXR knockout mice demonstrated better recovery following myocardial infarction through reduced apoptosis and fibrosis146.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [146]
In vitro studies on cardiomyocytes pinpoint FXR as a mediator of apoptosis through mitochondrial signaling.
“in vitro studies on cardiomyocytes pinpoint FXR as a mediator of apoptosis through mitochondrial signaling146.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [146]
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References 44 · Cited by 172
Research works printed but not linked: 1
- [13]Li Y Jadhav K Zhang Y Bile acid receptors in non-alcoholic fatty liver disease Biochem Pharmacol 86 1517 1524 23988487 PMC3925679
- Authors
- Xu, Y., Li, F., Zalzala, M., Xu, J., Gonzalez, F. J., Adorini, L., Lee, Y., Yin, L., & Zhang, Y.
- Affiliations
- Northeast Ohio Medical University (US)
- National Institutes of Health (US)
- University of Baghdad (IQ)
- Intercept Pharmaceuticals (United States) (US)
- Corresponding author
- Yin, Liya
- Zhang, Yanqiao
- ORCID
- Venue
- Hepatology
- Published
- 2016-07-30
- Volume
- 64
- Issue
- 4
- Pages
- 1072-1085
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC5033696
- OpenAlex
- W2485417128
- Cited by
- 172
- References
- 44
- Citations by year
- 2026: 17 · 2025: 17 · 2024: 22 · 2023: 16 · 2022: 27 · 2021: 23 · 2020: 7 · 2019: 14 · 2018: 13 · 2017: 15 · 2016: 1
- FWCI
- 15.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL103227)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK095895, R01DK102619)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- farnesoid X receptor, obeticholic acid, reverse cholesterol transport, intestinal cholesterol absorption, bile acid composition, taurocholate, muricholic acids, CYP7A1, CYP8B1, small heterodimer partner, sterol 12alpha-hydroxylase, atherosclerosis, fecal cholesterol excretion
- MeSH terms
- Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Biological Transport, Cholesterol, Intestinal Absorption, Mice, Inbred C57BL, Receptors, Cytoplasmic and Nuclear, Mice
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