Metabolic nuclear receptor signaling and the inflammatory acute phase response

Trends Endocrinol Metab. 2011 Aug;22(8):333-43. doi: 10.1016/j.tem.2011.04.004. Epub 2011 Jun 7.


The acute phase response (APR) classically refers to the rapid reprogramming of gene expression and metabolism in response to inflammatory cytokine signaling. As components of the innate immune system, hepatocyte-derived acute phase proteins (APPs) play a central role in restoring tissue homeostasis. Recently, an intriguing 'metaflammatory' facet of the APR became evident with chronically elevated APP levels being connected to metabolic syndrome disorders. The causality of these connections is unclear but could relate to adverse metabolic and inflammatory disturbances, particularly those affecting lipoprotein properties, cholesterol metabolism and atherogenesis. Here we review these aspects with an emphasis on the emerging importance of lipid-sensing nuclear receptors (LXRs, LRH-1, PPARs), in conjunction with anti-inflammatory transrepression pathways, as physiological and pharmacological relevant modulators of the APR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute-Phase Reaction / genetics
  • Acute-Phase Reaction / immunology
  • Acute-Phase Reaction / metabolism*
  • Adipose Tissue / immunology
  • Adipose Tissue / metabolism
  • Animals
  • Humans
  • Lipoproteins / genetics
  • Lipoproteins / metabolism
  • Liver / immunology
  • Liver / metabolism
  • Liver X Receptors
  • Orphan Nuclear Receptors / genetics
  • Orphan Nuclear Receptors / metabolism
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology*


  • Lipoproteins
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Peroxisome Proliferator-Activated Receptors
  • Receptors, Cytoplasmic and Nuclear