# Predominant protective role in hepatic steatosis and obesity by fish oil-derived furans

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $396,123

## Abstract

Project Summary
 Obesity is a growing global health burden that strongly associates with several comorbidities including non-
alcoholic fatty liver disease, hypertriglyceridemia, insulin resistance, and type 2 diabetes (T2D), reducing life
expectancy and quality. Fish oil is an important dietary component that provides essential omega-3 fatty acids
(Ω-3 FA) and is effective reducing severe hypertriglyceridemia. To better understand fish oil metabolites and
their effects, a metabolomics approach on urine and serum of healthy volunteers taking Lovaza, a clinical
grade FDA-approved omega-3 formulation, was performed. The furan CMPF was the major metabolite,
followed by several other furans and their glucuronides. To evaluate its effects, mice fed a high-fat diet were
administered CMPF to achieve levels equivalent to the ones observed in humans treated with Lovaza. CMPF
lowered plasma and liver triglycerides and reduced hepatic steatosis, recapitulating the effects reported both in
animals and in humans for Lovaza and fish oil treatments. The presence of furan fatty acids was confirmed in
both fish oil and Lovaza. Moreover, we found furan fatty acid to bind and inhibit hepatic acetyl-CoA
carboxylase, providing a mechanism of action. Based on these highly provocative preliminary results and
current understanding, we hypothesize that fish oil furans are significant bioactive compounds responsible for
fish oil-induced changes in hepatic lipid metabolism through acute modulation of metabolic pathways, in
particular, inhibition of acetyl-CoA carboxylase. This hypothesis will be tested by pursuing the following
Specific Aims
Aim 1: Define FuFA levels in Lovaza and FO, dose, exposure and pharmacokinetics.
Aim 2: Establish the role of FuFA on Lovaza-dependent TG reduction and NAFLD protection.
Aim 3: Define hepatic protein targets, metabolic effects and role of ACC on FuFA protective effects.
The development of mass spectrometry-based strategies to identify and characterize furans, application of
thermal shift assay to determine binding partners, synthetic strategies, lipidomic studies and metabolomic
assessments support a solid approach to definitively identify and characterize fish oil-derived bioactive furans.
Synthetic furan fatty acids will be tested in a rat model of diet-induced obesity and evaluated in the context of
Ω-3 FA. A successful completion of this proposal will have defined the participation and role of furans in the
beneficial effects described for fish oil. These are potent dietary ACC inhibitors present in fish oil at
pharmacologically relevant concentrations and are qualified impurities with a safe toxicological profile.
This proposal is designated to fill critical gaps in knowledge in Ω-3 FA therapeutics and can potentially re-
define current paradigms related to the impact of Ω-3 FA supplementation on lipogenesis, lipolysis, and
glycolysis.

## Key facts

- **NIH application ID:** 10133633
- **Project number:** 5R01DK112854-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Francisco Jose Schopfer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $396,123
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133633

## Citation

> US National Institutes of Health, RePORTER application 10133633, Predominant protective role in hepatic steatosis and obesity by fish oil-derived furans (5R01DK112854-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133633. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*