Retinoid metabolism and nuclear receptor responses: New insights into coordinated regulation of the PPAR-RXR complex

FEBS Lett. 2008 Jan 9;582(1):32-8. doi: 10.1016/j.febslet.2007.11.081. Epub 2007 Dec 7.

Abstract

Retinoids, naturally-occurring vitamin A derivatives, regulate metabolism by activating specific nuclear receptors, including the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). RXR, an obligate heterodimeric partner for other nuclear receptors, including peroxisome proliferator-activated receptors (PPARs), helps coordinate energy balance. Recently, many groups have identified new connections between retinoid metabolism and PPAR responses. We found that retinaldehyde (Rald), a molecule that can yield RA through the action of retinaldehyde dehydrogenases (Raldh), is present in fat in vivo and can inhibit PPAR gamma-induced adipogenesis. In vitro, Rald inhibits RXR and PPAR gamma activation. Raldh1-deficient mice have increased Rald levels in fat, higher metabolic rates and body temperatures, and are protected against diet-induced obesity and insulin resistance. Interestingly, one specific asymmetric beta-carotene cleavage product, apo-14'-carotenal, can also inhibit PPAR gamma and PPAR alpha responses. These data highlight how pathways of beta-carotene metabolism and specific retinoid metabolites may have direct distinct metabolic effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Mice
  • Peroxisome Proliferator-Activated Receptors / metabolism*
  • Retinoid X Receptors / metabolism*
  • Retinoids / metabolism*
  • Retinoids / pharmacology
  • Transcription, Genetic / drug effects

Substances

  • Peroxisome Proliferator-Activated Receptors
  • Retinoid X Receptors
  • Retinoids