Nitrated oleic acid up-regulates PPARgamma and attenuates experimental inflammatory bowel disease

Free Radic Biol Med. 2010 Feb 15;48(4):499-505. doi: 10.1016/j.freeradbiomed.2009.11.014. Epub 2009 Nov 20.


Nitric oxide and its metabolites undergo nitration reactions with unsaturated fatty acids during oxidative inflammatory conditions, forming electrophilic nitro-fatty acid derivatives. These endogenous electrophilic mediators activate anti-inflammatory signaling reactions, serving as high-affinity ligands for peroxisome proliferator-activated receptor gamma (PPARgamma). Here we examined the therapeutic effects of 9- or 10-nitro-octadecenoic oleic acid (OA-NO(2)) and native oleic acid (OA) in a mouse model of colitis. OA-NO(2) reduced the disease activity index and completely prevented dextran sulfate sodium-induced colon shortening and the increase in colonic p65 expression. Increased PPARgamma expression was observed in colon samples as well as in cells after OA-NO(2) administration, whereas no effect was seen with OA. This induction of PPARgamma expression was completely abolished by the PPARgamma antagonist GW9662. 5-Aminosalicylic acid, an anti-inflammatory drug routinely used in the management of inflammatory bowel disease, also increased PPARgamma expression but to a lesser extent. Altogether, these findings demonstrate that administration of OA-NO(2) attenuates colonic inflammation and improves clinical symptoms in experimental inflammatory bowel disease. This protection involves activation of colonic PPARgamma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques / methods
  • Fatty Acids / metabolism
  • Female
  • Free Radicals
  • Gene Expression Regulation, Enzymologic*
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / metabolism*
  • Mesalamine / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Models, Biological
  • Nitric Oxide / metabolism
  • Oleic Acid / metabolism
  • PPAR gamma / metabolism*
  • Up-Regulation*


  • Fatty Acids
  • Free Radicals
  • PPAR gamma
  • Oleic Acid
  • Nitric Oxide
  • Mesalamine