Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c

Mitsuhiro Watanabe, Sander M. Houten, Li Wang, Antonio Moschetta, David J. Mangelsdorf, Richard A. Heyman, David D. Moore, Johan Auwerx

Research output: Contribution to journalArticle

700 Citations (Scopus)

Abstract

We explored the effects of bile acids on triglyceride (TG) homeostasis using a combination of molecular, cellular, and animal models. Cholic acid (CA) prevents hepatic TG accumulation, VLDL secretion, and elevated serum TG in mouse models of hypertriglyceridemia. At the molecular level, CA decreases hepatic expression of SREBP-1c and its lipogenic target genes. Through the use of mouse mutants for the short heterodimer partner (SHP) and liver X receptor (LXR) α and β, we demonstrate the critical dependence of the reduction of SREBP-1c expression by either natural or synthetic farnesoid X receptor (FXR) agonists on both SHP and LXRα and LXRβ. These results suggest that strategies aimed at increasing FXR activity and the repressive effects of SHP should be explored to correct hypertriglyceridemia.

Original languageEnglish
Pages (from-to)1408-1418
Number of pages11
JournalJournal of Clinical Investigation
Volume113
Issue number10
DOIs
Publication statusPublished - 2004 Jan 1
Externally publishedYes

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Sterol Regulatory Element Binding Protein 1
Bile Acids and Salts
Cholic Acid
Triglycerides
Hypertriglyceridemia
Molecular Models
Liver
Homeostasis
Animal Models
Serum
Genes
Liver X Receptors

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Watanabe, M., Houten, S. M., Wang, L., Moschetta, A., Mangelsdorf, D. J., Heyman, R. A., ... Auwerx, J. (2004). Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. Journal of Clinical Investigation, 113(10), 1408-1418. https://doi.org/10.1172/JCI21025

Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. / Watanabe, Mitsuhiro; Houten, Sander M.; Wang, Li; Moschetta, Antonio; Mangelsdorf, David J.; Heyman, Richard A.; Moore, David D.; Auwerx, Johan.

In: Journal of Clinical Investigation, Vol. 113, No. 10, 01.01.2004, p. 1408-1418.

Research output: Contribution to journalArticle

Watanabe, M, Houten, SM, Wang, L, Moschetta, A, Mangelsdorf, DJ, Heyman, RA, Moore, DD & Auwerx, J 2004, 'Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c', Journal of Clinical Investigation, vol. 113, no. 10, pp. 1408-1418. https://doi.org/10.1172/JCI21025
Watanabe, Mitsuhiro ; Houten, Sander M. ; Wang, Li ; Moschetta, Antonio ; Mangelsdorf, David J. ; Heyman, Richard A. ; Moore, David D. ; Auwerx, Johan. / Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. In: Journal of Clinical Investigation. 2004 ; Vol. 113, No. 10. pp. 1408-1418.
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