Up-Regulation of UCP-2 Gene Expression by PPAR Agonists in Preadipose and Adipose Cells

• Published in: Biochemical and biophysical research communications Vol. 238; no. 2; pp. 606 - 611
• Main Authors: Aubert, Jérôme, Champigny, Odette, Saint-Marc, Perla, Negrel, Raymond, Collins, Sheila, Ricquier, Daniel, Ailhaud, Gérard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.09.1997
• Subjects: Adipocytes - cytology; Adipocytes - metabolism; Animals; Cell Differentiation - genetics; Cell Line; Epoprostenol - analogs & derivatives; Epoprostenol - pharmacology; Gene Expression Regulation - drug effects; Mice; Mitochondria - genetics; Mitochondria - metabolism; Palmitates - pharmacology; Receptors, Cytoplasmic and Nuclear - agonists; Thiazoles - pharmacology; Thiazolidinediones; Transcription Factors - agonists; Uncoupling Agents
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1997.7348

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, α-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 α-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 PPARδ in preadipose cells and the involvement of PPARγ2 in adipose cells in up-regulating UCP-2 gene expression. Thus, a potential link between fatty acid metabolism and thermogenesis may exist in PPAR-expressing tissues.