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Retinoid metabolism and nuclear receptor responses: New insights into coordinated regulation of the PPAR–RXR complex
Author(s) -
Ziouzenkova Ouliana,
Plutzky Jorge
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.11.081
Subject(s) - retinoid x receptor , nuclear receptor , peroxisome proliferator activated receptor , retinoid , retinoid x receptor alpha , adipogenesis , retinoic acid , receptor , biology , retinoid x receptor beta , medicine , endocrinology , biochemistry , chemistry , transcription factor , adipose tissue , gene
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 PPARγ‐induced adipogenesis. In vitro, Rald inhibits RXR and PPARγ 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 β‐carotene cleavage product, apo‐14′‐carotenal, can also inhibit PPARγ and PPARα responses. These data highlight how pathways of β‐carotene metabolism and specific retinoid metabolites may have direct distinct metabolic effects.