UP-REGULATION OF UCP-2 GENE-EXPRESSION BY PPAR AGONISTS IN PREADIPOSEAND 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 ti ssue may regulate UCP-2 gene expression. Since fatty acids act as posi tive transcriptional regulators of lipid-related genes by means of per oxisome proliferator-activated receptors (PPARs), the regulation of UC P-2 gene expression by PPAR agonists (carbacyclin, alpha-bromopalmitat e, BRL49653) has been examined in mouse preadipose and adipose cells i n primary cultures or from clonal lines (Ob1771, 3T3-F442A, 1B8). In p readipose cells, carbacyclin and alpha-bromopalmitate are active and B RL49653 shows no effect, whereas all these ligands are active in adipo se cells. The stimulatory effect of PPAR agonists is potentiated by RX R agonists in adipose cells. In contrast to the UCP-1 gene, norepineph rine 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. betwee n fatty acid metabolism and thermogenesis may exist in PPAR-expressing tissues. (C) 1997 Academic Press.