Polyunsaturated fatty acids stimulate hepatic UCP-2 expression via a PPARalpha-mediated pathway.


Journal Article

The discovery of homologs of the brown fat uncoupling protein(s) (UCP) UCP-2 and UCP-3 revived the hypothesis of uncoupling protein involvement in the regulation of energy metabolism. Thus we hypothesized that UCP-2 would be regulated in the hepatocyte by fatty acids, which are known to control other energy-related metabolic processes. Treatment with 250 microM palmitic acid was without effect on UCP-2 expression, whereas 250 microM oleic acid exhibited a modest eightfold increase. Eicosapentaenoic acid (EPA), a polyunsaturated fatty acid, exerted a 50-fold upregulation of UCP-2 that was concentration dependent. This effect was seen within 12 h and was maximal by 36 h. Aspirin blocked the induction of UCP-2 by EPA, indicating involvement of the prostaglandin pathway. Hepatocytes treated with arachidonic acid, the immediate precursor to the prostaglandins, also exhibited an aspirin-inhibitable increase in UCP-2 levels, further supporting the involvement of prostaglandins in regulating hepatic UCP-2. The peroxisome proliferator-activated receptor-alpha (PPARalpha) agonist Wy-14643 stimulated UCP-2 mRNA levels as effectively as EPA. These data indicate that UCP-2 is upregulated by polyunsaturated fatty acids, potentially through a prostaglandin/PPARalpha-mediated pathway.

Full Text

Cited Authors

  • Armstrong, MB; Towle, HC

Published Date

  • December 2001

Published In

Volume / Issue

  • 281 / 6

Start / End Page

  • E1197 - E1204

PubMed ID

  • 11701434

Pubmed Central ID

  • 11701434

Electronic International Standard Serial Number (EISSN)

  • 1522-1555

International Standard Serial Number (ISSN)

  • 0193-1849

Digital Object Identifier (DOI)

  • 10.1152/ajpendo.2001.281.6.e1197


  • eng