Regulation of hepatic Insig-2 by the farnesoid X receptor.

Regulation of hepatic Insig-2 by the farnesoid X receptor. Research Abstract Details 

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Regulation of hepatic Insig-2 by the farnesoid X receptor. Abstract Text:

Melissa L Hubbert,Yanqiao Zhang,Florence Y Lee,Peter A Edwards,

Activation of the farnesoid X receptor (FXRalpha) affects genes controlling many pathways, including those involved in bile acid and glucose homeostasis. Here we report that a critical gene involved in cholesterol homeostasis, Insig-2, was induced when mice or cultured cells were treated with FXRalpha agonists or infected with constitutively active FXRalpha. No such induction was observed in agonist-treated FXRalpha-/- mice. Further analysis, which included EMSAs, reporter gene activation, and chromatin immunoprecipitation, identified two functional FXRalpha response elements within intron 2 of the mouse Insig-2 gene. In addition to increasing hepatic Insig-2 protein levels in wild-type mice, FXRalpha activation also reduced lanosterol 14alpha-demethylase mRNA levels and 3-hydroxy-3-methylglutaryl-coenzyme A reductase protein levels. Together, these changes likely account for the decrease in cholesterol synthesis observed after activation of FXR in primary hepatocytes. In conclusion, the current study links hepatic FXRalpha activation to regulation of genes involved in cholesterol synthesis.

Regulation of hepatic Insig-2 by the farnesoid X receptor. Publishing Authors By Initials

ML Hubbert,Y Zhang,FY Lee,PA Edwards,

For similar proteins: transcription factors research abstracts see: proteins: transcription factors research

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Regulation of hepatic Insig-2 by the farnesoid X receptor. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular endocrinology (Baltimore, Md.)

VOLUME: 21

Page Numbers: 1359-69

Journal Abbreviation: Mol. Endocrinol.

ISSN: 0888-8809

DAY: 17

MONTH: 04

YEAR: 2007

Regulation of hepatic Insig-2 by the farnesoid X receptor. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8801431

Regulation of hepatic Insig-2 by the farnesoid X receptor. Keywords Mesh Terms:

KEYWORDS: Transcription Factors

MESH TERMS: metabolism

Chemical & Substance for Abstract: Regulation of hepatic Insig-2 by the farnesoid X receptor. Information

Substance Name: lanosterol 14 alpha-demethylase

Registry Number: EC 1.14.13.70

Grant and Affiliation Information for Regulation of hepatic Insig-2 by the farnesoid X receptor.

AFFILIATION: Department of Biological Chemistry, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL68445

ACRONYM: HL

MEDLINETA: Mol Endocrinol

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