# Formation and metabolism of nitrated fatty acids

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $394,895

## Abstract

Project Summary
 Nitro-fatty acids (NO2-FA) are endogenous adaptive signaling mediators present in animal and human
tissues and fluids under basal conditions. They are formed at sites of inflammation and, most importantly, as an
interaction of dietary components containing nitrite and nitrate (e.g. leafy vegetables) and conjugated fatty acids
(e.g. dairy products, and plant seeds). NO2-FA are electrophilic and pleiotropic signaling modulators that have
demonstrated protective effects in various pathological conditions. They exert their signaling actions by reacting
with target proteins to activate Nrf2 and heat shock protein expression, inhibit NF-κB and STING inflammatory
signaling, and associated fibrotic events. During the R0, we discovered the presence of a new group of nitrated
species, NO2-conjugated linolenic acid (NO2-CLNA), in healthy human urines. These lipids contribute to 40% of
the total NO2-FA pool, despite the limited levels of the CLNA substrate present in the western diet. The
remarkable nitration yields and ease of nitration of CLNA under biological conditions, the levels detected in
humans, and the potential biological activities underscore the value of this proposal. We hypothesize that the
nitration of CLNA is a critical reaction in the gastric compartment that confers new metabolic, protective, and
anti-inflammatory functions to these conjugated fatty acids. We will test the hypothesis through the following
Aims:
Aim #1 Define the NO2-CLnA formation and absorption.
Aim #2 Define the reactivity, signaling properties, and metabolism of new bioactive NO2-CLNA
Through quantitative and mechanistic studies, this proposal has the potential to change the CLA and CLNA
paradigm and demonstrate an active role for nitration in conferring new signaling activities to these conjugated
fatty acids, impacting how we understand pharmacology of these dietary fatty acids.

## Key facts

- **NIH application ID:** 10388616
- **Project number:** 2R01GM125944-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Francisco Jose Schopfer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $394,895
- **Award type:** 2
- **Project period:** 2017-12-10 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388616

## Citation

> US National Institutes of Health, RePORTER application 10388616, Formation and metabolism of nitrated fatty acids (2R01GM125944-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10388616. Licensed CC0.

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