nitrofatty

Nitro-fatty acids, also called NO2-fatty acids, are nitrated derivatives of polyunsaturated fatty acids that occur naturally in mammals. They exist primarily as nitroalkenes in which a nitro group is added to a carbon–carbon double bond of fatty acids such as oleic, linoleic, arachidonic, and docosahexaenoic acids. Common endogenous examples include nitro-oleic acid (NO2-OA), nitro-linoleic acid (NO2-LA), nitro-arachidonic acid (NO2-AA), and nitro-docosahexaenoic acid (NO2-DHA).

Formation and occurrence

NO2-FAs form in vivo under nitrosative and inflammatory conditions when reactive nitrogen species react with polyunsaturated fatty acids. They have been detected in plasma and various tissues, including liver, adipose, and vascular compartments, and can arise from endogenous signaling pathways as well as experimental or dietary sources.

Chemical properties and mechanism of action

The nitro group creates an electrophilic nitroalkene moiety, which can undergo Michael-type addition with nucleophilic sites such as cysteine thiols on proteins. This covalent modification can alter protein function and signaling networks. NO2-FAs are thus considered signaling mediators that can influence redox biology and post-translational regulation.

Biological significance

NO2-FAs modulate inflammation and metabolism. They can activate peroxisome proliferator-activated receptors (PPAR-α and PPAR-γ) and inhibit NF-κB–driven inflammatory signaling. In experimental models, they affect glucose and lipid metabolism, vascular function, and cytoprotective pathways, linking nitrosative stress to adaptive cellular responses.

Detection and research

NO2-FAs are measured using lipidomics methods, typically liquid chromatography–mass spectrometry. Synthetic nitro-fatty acids are used to study signaling mechanisms, physiological roles, and potential therapeutic applications.

Therapeutic potential

Research explores NO2-FAs as anti-inflammatory and metabolic regulators, with interest in cardiovascular and metabolic disease contexts. Clinical use remains experimental, emphasizing their signaling capacity and endogenous relevance.