# Lipoprotein Lipase Through the Secretory System

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $381,519

## Abstract

Abstract:
Lipoprotein lipase (LPL) reduces triglyceride levels in the blood. Elevated triglyceride levels are a
risk factor for heart disease, and triglyceride levels are correlated with insulin resistance in diabetic
individuals. Here, we aim to better understand an underappreciated aspect of LPL biology: most
of the LPL that is synthesized never makes it out of the cell. Some of this LPL misfolds and can’t
escape endoplasmic reticulum (ER) quality control. Additionally, some fully functional LPL is
stored in poorly defined secretory vesicles at the periphery of the cell, and this LPL is degraded if
cellular signals do not trigger its release. The ER-resident membrane protein Lipase Maturation
Factor 1 (LMF1) aids in LPL folding in, and exit from, the ER. Our studies have shown that LMF1
helps to ensure LPL’s disulfide bonds are correctly processed. We don’t know the mechanism by
which LMF1 aids in LPL disulfide bond processing, and in Aim 1 we will study LMF1’s structure
and function. With respect to the trafficking of LPL stored in secretory vesicles, studies to date
indicate that, in adipose tissue, this LPL is secreted in response to insulin signaling. However, we
do not fully understand the trafficking itinerary that mobilizes stored LPL for secretion from the
cell in response to insulin. In Aim 2, we will explore how vesicles containing stored LPL are
selected, mobilized, and released after insulin signaling. Together, these two aims will define the
factors and mechanisms that contribute to ensuring LPL’s exit from the cell to the circulation where
it can lower triglycerides. Defining these mechanisms will suggest new ways to lower triglycerides
and the burden of diabetes and heart disease.

## Key facts

- **NIH application ID:** 10756550
- **Project number:** 5R01HL163352-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Saskia Neher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $381,519
- **Award type:** 5
- **Project period:** 2022-12-21 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10756550

## Citation

> US National Institutes of Health, RePORTER application 10756550, Lipoprotein Lipase Through the Secretory System (5R01HL163352-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10756550. Licensed CC0.

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