# Fatty Acids: Ischemic Protection and Repair

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $594,548

## Abstract

The heart reduces fatty acid (FAs) oxidation and switches to greater glucose utilization with ischemia. While
this process allows more ATP production with less oxygen use, it occurs at the expense of limiting the use of
FAs, the major substrates for cardiac energy. We hypothesize that this leads to fuel deprivation, especially as
blood flow reduction decreases energetic substrate availability. If this hypothesis is correct, then storage of
more triglyceride in the heart would lead to reduced ischemic damage; this we speculate is the reason for the
“obesity paradox” in which obese humans who have more ischemic disease also have increased post
myocardial infarction survival.
 This proposal includes experiments to study basic and clinically relevant relationships between heart
FA metabolism and heart function. Specifically, we will use mice created by the PI to study how changes in
triglyceride stores and lipid uptake alter cardiac response to ischemia/reperfusion. In addition, we will test
whether deletion of genes required for normal uptake of FAs by myeloid cells affects their conversion to an
alternatively activated and reparative phenotype. These studies will include assessment of cardiac gene
changes and lipidomics and will utilize tracer kinetics to assess uptake and oxidation of glucose and lipids, and
to determine their downstream products. The experiments will require the collaboration of two laboratories: one
with expertise in heart lipid metabolism and the second with expertise in ischemic/reperfusion models and
analysis of substrate metabolism. The three aims of this application are the following: Aim 1. To determine
whether increased cardiomyocyte storage of triglyceride improves response to ischemia. Aim 2. To assess
whether mice with reduced heart lipid uptake have altered response to ischemia. Aim 3. To assess ischemic
injury and repair in mice with macrophage-specific deletions of lipoprotein lipase and cluster of differentiation
(CD)36. The experiments will use several lines greater cardiac triglyceride stores due to transgenic expression
of diacylglycerol acyl transferase 1 and peroxisomal proliferator activated receptor γ, and mice with reduced
uptake of FAs due to tissue specific deletions of lipoprotein lipase and CD36. These studies will illustrate
possible metabolic approaches to reducing ischemic injury and improving repair of damaged myocardium.

## Key facts

- **NIH application ID:** 9891096
- **Project number:** 5R01HL135987-04
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Ira J Goldberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $594,548
- **Award type:** 5
- **Project period:** 2017-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891096

## Citation

> US National Institutes of Health, RePORTER application 9891096, Fatty Acids: Ischemic Protection and Repair (5R01HL135987-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9891096. Licensed CC0.

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