Retinoid metabolism and nuclear receptor responses: New insights into coordinated regulation of the PPAR-RXR complex.
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.
Ziouzenkova
Ouliana
O
Department of Human Nutrition, Ohio State University, Columbus, OH 43210, USA.
Plutzky
Jorge
J
D000818:Animals; D051379:Mice; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D047488:Retinoid X Receptors / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D047492:Peroxisome Proliferator-Activated Receptors; D047488:Retinoid X Receptors; D012176:Retinoids