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FXR activation prot...
FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption
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Clifford, B. L. (author)
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Sedgeman, L. R. (author)
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Williams, K. J. (author)
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Morand, P. (author)
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Cheng, A. (author)
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Jarrett, K. E. (author)
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Chan, A. P. (author)
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Brearley-Sholto, M. C. (author)
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- Wahlström, Annika, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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Ashby, J. W. (author)
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Barshop, W. (author)
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Wohlschlegel, J. (author)
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Calkin, A. C. (author)
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Liu, Y. Y. (author)
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- Thorell, A. (author)
- Karolinska Institutet
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Meikle, P. J. (author)
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Drew, B. G. (author)
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Mack, J. J. (author)
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- Marschall, Hanns-Ulrich, 1954 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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Tarling, E. J. (author)
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Edwards, P. A. (author)
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Vallim, T. Q. D. (author)
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 33:8
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Abstract
Subject headings
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- FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive lipidomic analyses, we show that FXR activation in mice or humans specifically reduces hepatic levels of mono-and polyunsaturated fatty acids (MUFA and PUFA). Decreases in MUFA are due to FXR-dependent repression of Scd1, Dgat2, and Lpin1 expression, which is independent of SHP and SREBP1c. FXR-dependent decreases in PUFAs are mediated by decreases in lipid absorption. Replenishing bile acids in the diet prevented decreased lipid absorption in GSK2324-treated mice, suggesting that FXR reduces absorption via decreased bile acids. We used tissue-specific FXR KO mice to show that hepatic FXR controls lipogenic genes, whereas intestinal FXR controls lipid absorption. Together, our studies establish two distinct pathways by which FXR regulates hepatic lipids.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- farnesoid-x-receptor
- fatty liver-disease
- small heterodimer partner
- beta-muricholic acid
- nuclear receptor
- metabolism
- binding
- cholesterol
- Cell Biology
- Endocrinology & Metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Clifford, B. L.
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Sedgeman, L. R.
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Williams, K. J.
-
Morand, P.
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Cheng, A.
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Jarrett, K. E.
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show more...
-
Chan, A. P.
-
Brearley-Sholto, ...
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Wahlström, Annik ...
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Ashby, J. W.
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Barshop, W.
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Wohlschlegel, J.
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Calkin, A. C.
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Liu, Y. Y.
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Thorell, A.
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Meikle, P. J.
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Drew, B. G.
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Mack, J. J.
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Marschall, Hanns ...
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Tarling, E. J.
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Edwards, P. A.
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Vallim, T. Q. D.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Cell Metabolism
- By the university
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University of Gothenburg
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Karolinska Institutet