# Engineering the release of oxylipins through the skin

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $616,063

## Abstract

PROJECT SUMMARY/ABSTRACT
Obesity and type 2 diabetes are increasing dramatically worldwide. Recent data has shown that obesity rates
have more than doubled since 1980 and if these trends continue unabated, by 2030 estimates predict that
approximately half the U.S. population will be obese, with 25% developing type 2 diabetes. Adipose tissue is
an important site for initiation and aggravation of obesity and type 2 diabetes because it is a key endocrine
organ that functions to maintain energy homeostasis, and recent studies have identified lipokines, or signaling
lipids, released from adipose tissue as molecules that can mediate metabolic effects. One class of these
lipokines are oxylipins, oxidized lipid metabolites that exert metabolic effects. An important oxylipin for
metabolic control is the linoleic acid metabolite 12,13-diHOME, which is released from brown adipose tissue
(BAT) in response to cold and exercise in rodents and humans and beneficially impacts glucose and fatty acid
metabolism. 12,13-diHOME increases fatty acid uptake into brown adipose tissue, skeletal muscle, and
cardiomyocytes, and is negatively correlated with circulating triglycerides and BMI in humans. However, due to
its very short half-life, systemic regulation is difficult to maintain and thus its therapeutic potential has not been
fully realized. To address this essential issue, we developed a paradigm-shifting approach to increase 12,13-
diHOME via tissue nanotransfection (TNT), a non-viral gene delivery technology with high translational
potential. TNT delivery of the genes Ephx1/2, coding for the enzymes that make bioactive 12,13-diHOME
results in a sustained systemic increase of 12,13-diHOME in circulation and corresponds to reduced adiposity
and improved metabolic health. In these proposed studies we will optimize a therapeutic upregulation of
Ephx1/2 via TNT in pre-clinical models and comprehensively establish the physiological ramifications of a
sustained systemic increase in 12,13-diHOME and provide new therapeutic approaches to combat obesity and
type 2 diabetes. We will do this using the following two specific aims: 1) Determine the effectiveness,
efficiency, and mechanisms through which TNT-based delivery of Ephx1/2 into the skin increases 12,13-
diHOME in circulation and; 2) Determine the physiological ramifications of a sustained increase in the oxylipin
12,13-diHOME by TNT. The proposed studies have the potential to provide paradigm-shifting results and
elucidate novel mechanisms to sustain oxylipin up-regulation and providing new therapeutic approaches to
combat obesity and type 2 diabetes.

## Key facts

- **NIH application ID:** 10836028
- **Project number:** 5R01DK133859-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Daniel Gallego-Perez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $616,063
- **Award type:** 5
- **Project period:** 2023-05-05 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836028

## Citation

> US National Institutes of Health, RePORTER application 10836028, Engineering the release of oxylipins through the skin (5R01DK133859-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10836028. Licensed CC0.

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