Molecular biology and functional genomics of liver X receptors (LXR) in relationship to metabolic diseases

Curr Opin Pharmacol. 2010 Dec;10(6):692-7. doi: 10.1016/j.coph.2010.07.003. Epub 2010 Sep 9.

Abstract

The metabolic syndrome constitutes a group of metabolic conditions that increase the risk of developing diseases, including cardiovascular disease (CVD) and type 2 diabetes (T2D). LXRα/β are regulators of lipogenesis, cholesterol/glucose homoeostasis and inflammatory pathways, processes that are intertwined with development of the metabolic syndrome. The employment of LXRs as pharmaceutical targets for treatment of various aspects of the metabolic syndrome has been promptly investigated but serious side effects, like hepatic steatosis, have hampered this process. Novel treatment regimes now focus on development of isoform-specific or tissue-specific LXR agonist/antagonist compounds to circumvent effects on lipid biosynthesis. Other strategies to explore the beneficial aspects of LXR activation include targeting co-factors or pathways that are modifying LXR activity.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / metabolism
  • Cholesterol / metabolism
  • DNA-Binding Proteins / metabolism
  • Glucose Metabolism Disorders / genetics
  • Glucose Metabolism Disorders / metabolism
  • Humans
  • Inflammation / metabolism
  • Lipogenesis
  • Liver X Receptors
  • Metabolic Diseases / drug therapy*
  • Metabolic Diseases / metabolism*
  • Metabolic Syndrome / metabolism
  • Mice
  • Mice, Mutant Strains
  • Molecular Targeted Therapy
  • Orphan Nuclear Receptors / genetics*
  • Orphan Nuclear Receptors / metabolism*
  • Protein Isoforms / metabolism

Substances

  • DNA-Binding Proteins
  • Liver X Receptors
  • NR1H3 protein, human
  • Nr1h3 protein, mouse
  • Orphan Nuclear Receptors
  • Protein Isoforms
  • Cholesterol