Olives and Olive Oil Are Sources of Electrophilic Fatty Acid Nitroalkenes

Abstract

Extra virgin olive oil (EVOO) and olives, key sources of unsaturated fatty acids in the Mediterranean diet, provide health benefits to humans. Nitric oxide (•NO) and nitrite (NO2 −)-dependent reactions of unsaturated fatty acids yield electrophilic nitroalkene derivatives (NO2-FA) that manifest salutary pleiotropic cell signaling responses in mammals. Herein, the endogenous presence of NO2-FA in both EVOO and fresh olives was demonstrated by mass spectrometry. The electrophilic nature of these species was affirmed by the detection of significant levels of protein cysteine adducts of nitro-oleic acid (NO2-OA-cysteine) in fresh olives, especially in the peel. Further nitration of EVOO by NO2 − under acidic gastric digestive conditions revealed that human consumption of olive lipids will produce additional nitro-conjugated linoleic acid (NO2-cLA) and nitro-oleic acid (NO2-OA). The presence of free and protein-adducted NO2-FA in both mammalian and plant lipids further affirm a role for these species as signaling mediators. Since NO2-FA instigate adaptive anti-inflammatory gene expression and metabolic responses, these redox-derived metabolites may contribute to the cardiovascular benefits associated with the Mediterranean diet.

Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase

“…Despite the Mediterranean diet being rich in fats that might promote cardiovascular disease, it protects against hypertension and associated risks (28). A key feature of the Mediterranean diet is the coconsumption of nitrite together with unsaturated fatty acid (e.g., from green leafy vegetables eaten with olive oil), promoting the further formation of sEH-inhibitory electrophilic fatty acid nitroalkenes that are also endogenously present in olives and olive oils (21). Indeed, when an unsaturated fatty acid was coadministered with sodium nitrite, using a protocol that elevates tissue nitro fatty acid levels (40), there was significant inhibition of sEH in WT but not KI mice.…”

“…Nitro fatty acids, which have been detected endogenously in plasma and urine of humans, animal models, and plants (19)(20)(21), mediate salutary cardiovascular signaling actions (22). For example they relax blood vessels, attenuate platelet activation, and reduce inflammation via cyclic guanosine monophosphate (cGMP)-independent mechanisms (23,24).…”

Nitro-fatty acid pharmacokinetics in the adipose tissue compartment

“…Wherever possible, the maximum area for each tissue within a single autoradiogram was defined for measurement. These radiolabeling experiments were conducted at Huntingdon Life Sciences (Cambridgeshire, and extra virgin olive oil (15,16). Notably, plasma and urinary NO 2 -FA concentrations in humans are increased following oral supplementation with NO 2  , nitrate (NO 3  ), and conjugated linoleic acid (CLA) (17,18 18 ]OA) were synthesized by direct alkene nitroselenation of the corresponding native FAs, as previously described (21).…”

The Chemical Basis of Thiol Addition to Nitro-conjugated Linoleic Acid, a Protective Cell-signaling Lipid

“…Nitroalkene fatty acids exhibit potent anti-inflammatory and cyto-protective properties and thus are beneficial in many models of disease, including atherosclerosis, restenosis, ischemia reperfusion, renal injury, diabetes, metabolic syndrome, and endotoxemia (6 -13). Furthermore, endogenous formation of nitroalkene fatty acids has been associated with the cardioprotective effects of the Mediterranean diet (14,15). Notably, the potential application of soft electrophiles as pharmacological agents is underscored by the Food and Drug Administration approval of dimethyl fumarate for the treatment of multiple sclerosis (16,17).…”