# Molecular mechanisms of intra- and inter-cellular fatty acid trafficking

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $380,880

## Abstract

ABSTRACT
Fatty acids are essential cellular lipids. They allow cells to store energy in a highly concentrated form and to
build the membranes that separate cells from their environment. Both impaired and excess lipid storage can
lead to human disease: failure to appropriately store fat leads to lipodystrophy and cachexia, while excess
lipid storage is a hallmark of metabolic syndrome, type 2 diabetes, atherosclerosis, and fatty liver disease.
The goal of our research is to address two fundamental questions about fatty acid trafficking. The first of
these is: how do fatty acids traffic among organelles within a cell? Fatty acids are stored as triglycerides
within organelles called lipid droplets. Emerging evidence indicates that fatty acids can transfer between
lipid droplets and other organelles at sites of close apposition called membrane contact sites. However, the
proteins that mediate lipid droplet-organelle contact sites are largely unknown. We will use candidate and
unbiased approaches to identify proteins that mediate lipid droplet-organelle contact sites. We will then test
the effect of modulating these proteins on fatty acid storage, trafficking, and metabolism. When organelle
dynamics and fatty acid metabolism within a cell are impaired, cells may efflux excess fatty acids to their
neighbors. Thus, the second question we will address is: how do fatty acids traffic between cells in a tissue?
Several possible mechanisms exist, including direct transfer at cell-cell contacts; efflux of “free fatty acids”
followed by uptake into a neighboring cell; and transfer of fatty acids via particles including lipoprotein
particles and exosomes. We will investigate the mechanisms of intercellular fatty acid trafficking in response
to nutrient deprivation and between different cell types. To address these questions, we will use a
combination of techniques including molecular biology, biochemistry, cutting-edge multispectral and super
resolution microscopy, and advanced image analysis approaches. Together, these studies will elucidate
molecular mechanisms of fatty acid trafficking within and between cells, in response to changing
environmental and developmental conditions. A better understanding of these mechanisms will have
implications for both diseases of impaired and excess lipid storage.

## Key facts

- **NIH application ID:** 10164808
- **Project number:** 5R35GM133460-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Sarah Cohen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $380,880
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164808

## Citation

> US National Institutes of Health, RePORTER application 10164808, Molecular mechanisms of intra- and inter-cellular fatty acid trafficking (5R35GM133460-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10164808. Licensed CC0.

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