Retinoic acid activation of peroxisome proliferation-activated receptor delta represses obesity and insulin resistance.
Retinoic acid (RA) was found to be a ligand for peroxisome proliferation-activated receptor delta (PPARdelta) as well as the classical RA receptor (RAR). Carrier proteins that move the RA from the cytosol into the nucleus are the fatty acid-binding protein 5 (FABP5), activating PPARdelta, and the cellular retinoic acid-binding protein II (CRABPII), activating RAR. The ratio of FABP5/CRABPII concentrations determines which receptor is activated. By activating PPARdelta, RA was found to induce expression of genes affecting lipid and glucose homeostasis, in particular, leading to expression of the insulin-signaling gene PDK1 and improvement of insulin action. Hence, RA stimulates lipolysis and reduces triglyceride content. In vivo, obesity has led to downregulation of adipose PPARdelta expression. RA implantation into obese mice has caused upregulation of levels of PPARdelta and consequent weight loss as well as increased expression of PPARdelta target genes, including the insulin-signaling gene PDK1.
Wolf
George
G
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California, USA. nutritionreviews@ilsi.org
D000818:Animals; D004789:Enzyme Activation; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008024:Ligands; D050356:Lipid Metabolism; D009765:Obesity / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D047494:PPAR delta; D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin