Up-regulation of UCP-2 gene expression by PPAR agonists in preadipose and adipose cells

UCP-2 is a member of the emerging family of UCP homologues. Upon high-fat feeding, UCP-2 mRNA levels are increased in epididymal fat pads of A/J mice, suggesting that the flux of fatty acids entering adipose tissue may regulate UCP-2 gene expression. Since fatty acids act as positive transcriptional regulators of lipid-related genes by means of peroxisome proliferator-activated receptors (PPARs), the regulation of UCP-2 gene expression by PPAR agonists (carbacyclin, alpha-bromopalmitate, BRL49653) has been examined in mouse preadipose and adipose cells in primary cultures or from clonal lines (Ob1771, 3T3-F442A, 1B8). In preadipose cells, carbacyclin and alpha-bromopalmitate are active and BRL49653 shows no effect, whereas all these ligands are active in adipose cells. The stimulatory effect of PPAR agonists is potentiated by RXR agonists in adipose cells. In contrast to the UCP-1 gene, norepinephrine as a cAMP-elevating agent does not enhance the expression of UCP-2 gene. Altogether, the data favor a predominant role of PPAR delta in preadipose cells and the involvement of PPAR gamma 2 in adipose cells in upregulating UCP-2 gene expression. Thus, a potential link. between fatty acid metabolism and thermogenesis may exist in PPAR-expressing tissues. (C) 1997 Academic Press.