Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 16 No. 5 • May 2013


Nitrated Fatty Acids

Nitrated Fatty Acids Are Natural Metabolites
That Mediate Anti-Inflammatory Signals

For some time, there have been papers published on the anti-inflammatory and vasorelaxation activity of nitrated fatty acids.1–4 Now, a new paper5 reports that “conjugated linoleic acid (CLA) is the preferential unsaturated fatty acid substrate for nitration reactions during oxidative conditions and digestion.” It is reported that “multiple enzymatic and cellular mechanisms account for CLA nitration, including reactions catalyzed by mitochondria, activated macrophages, and gastric acidification.”5 It is reported here that CLA yields up to 105 greater extent of nitration products as compared to it’s natural competitor bis-allylic linoleic acid.

The nitrated fatty acids act as a circulating reservoir of nitrite for local conversion to nitric oxide. Hence, it is a way to increase nitric oxide availability throughout the body.

“Dietary CLA and nitrite supplementation [which can be derived from nitrate-rich foods such as spinach] in rodents elevates NO2–CLA levels in plasma, urine, and tissues, which in turn induces heme oxygenase-1 (HO-1) [an important antiinflammatory enzyme] expression in the colonic epithelium.” Incredibly, in human coronary artery endothelium, the paper notes, fatty acid nitroalkenes significantly influence the expression of ~400 metabolic and anti-inflammatory-related genes, including important inflammation regulators such as PPARgamma, Keap1/Nrf2, heat shock factor-1, and NF-kappaB. According to the authors, NO (nitric oxide) doesn’t directly nitrate protein or lipids, but must be oxidized to the proximal nitrating species NO2. “Importantly, NO2– [nitrite]-supplemented diets are associated with a variety of beneficial anti-inflammatory and metabolic actions, including the regulation of mitochondrial function, adipogenesis, oxygen delivery to tissues, and blood pressure. Although these events can in part be attributed to the generation of NO [nitric oxide], salutary responses to NO2–-derived oxides of nitrogen may also be transduced by the concomitant generation of electrophilic nitro-fatty acids (NO2–FA).”5

The Bottom Line

In this new paper5 the researchers show that CLA is the preferential endogenous fatty acid substrate for fatty acid nitration by NO and NO2– and provides tissue-protective and anti-inflammatory actions. Beneficial effects reported in the paper for nitrated fatty acids included: in mouse models of metabolic and inflammatory injury, fatty acid nitroalkene administration at nanomolar concentrations prevents restenosis after blood vessel injury, in mouse models of metabolic syndrome, nitrated fatty acids limit weight gain and loss of insulin sensitivity, nitrated fatty acids protect against ischemia-reperfusion injury, reduces plaque formation in a rodent model of atherosclerosis, and inhibits the onset of chemically induced inflammatory bowel disease. So, although the two of us do not use high-dose CLA for purported weight control, we do consider it’s use at lower, more physiological doses for the formation of nitrated-CLA as reported here5 to be potentially important.

References

  1. Baker et al. Fatty acid transduction of nitric oxide signaling. J Biol Chem. 280(51):42464-75 (2005).
  2. Lima et al. Nitrated lipids decompose to nitric oxide and lipid radicals and cause vasodilation. Free Radic Biol Med. 39:532-9 (2005).
  3. Trostchansky and Rubbo. Nitrated fatty acids: mechanisms of formation, chemical characterization, and biological properties. Free Radic Biol Med. 44:1887-96 (2008).
  4. Tsikas et al. Nitro-fatty acids occur in human plasma in the picomolar range: a targeted nitro-lipidomics GC-MS/MS study. Lipids. 44:855-65 (2009).
  5. Bonacci et al. Conjugated linoleic acid is a preferential substrate for fatty acid nitration. J Biol Chem. 287(53):44071-82 (2012).

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