Regulation of FXR transcriptional activity in health and disease: Emerging roles of FXR cofactors and post-translational modifications

Research output: Contribution to journalReview articlepeer-review

Abstract

Abnormally elevated lipid and glucose levels due to the disruption of metabolic homeostasis play causative roles in the development of metabolic diseases. A cluster of metabolic conditions, including dyslipidemia, abdominal obesity, and insulin resistance, is referred to as metabolic syndrome, which has been increasing globally at an alarming rate. The primary nuclear bile acid receptor, Farnesoid X Receptor (FXR, NR1H4), plays important roles in controlling lipid and glucose levels by regulating expression of target genes in response to bile acid signaling in enterohepatic tissues. In this review, I discuss how signal-dependent FXR transcriptional activity is dynamically regulated under normal physiological conditions and how it is dysregulated in metabolic disease states. I focus on the emerging roles of post-translational modifications (PTMs) and transcriptional cofactors in modulating FXR transcriptional activity and pathways. Dysregulation of nuclear receptor transcriptional signaling due to aberrant PTMs and cofactor interactions are key determinants in the development of metabolic diseases. Therefore, targeting such abnormal PTMs and transcriptional cofactors of FXR in disease states may provide a new molecular strategy for development of pharmacological agents to treat metabolic syndrome. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.

Original languageEnglish (US)
Pages (from-to)842-850
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1812
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • Acetylation
  • Bile acid
  • Chromatin
  • Cofactor
  • Metabolic syndrome
  • Phosphorylation
  • Post-translational modification

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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