# The Molecular Regulation of Lipoprotein Lipase Activity

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $22,712

## Abstract

Abstract
Heart disease is the leading cause of mortality worldwide. One significant risk factor for developing heart disease
is uncontrolled high circulating triglycerides. The enzyme Lipoprotein Lipase (LPL) hydrolyzes triglycerides
packaged in circulating lipoprotein particles. For this reason, LPL activity and levels are closely correlated with
the risk of developing cardiovascular disease. Understanding LPL regulation is important for understanding the
role of LPL in disease. The transcriptional regulation of the LPL gene has been well characterized. LPL is
synthesized in the parenchyma of tissues including adipose and muscle and its transcription is tightly regulated.
Post-translationally, LPL is thought to be stored in secretory vesicles and released by unidentified physiological
cues. LPL from intracellular stores is actively degraded in lysosomes. It is not clear how this LPL is targeted for
degradation as opposed to secretion. One clue to this regulation comes from Type 2 Diabetes (T2D). Insulin
signaling is essential for normal LPL activity and patients with insulin resistance experience reduced LPL activity.
We hypothesize that insulin influences LPL stability to regulate its trafficking. The objective of this proposal is to
understand the molecular mechanisms of LPL trafficking in adipocytes. In aim 1, we will examine the intracellular
trafficking and degradation of LPL in adipose tissue. In aim 2 we will describe the role of Tankyrase 1 in LPL
trafficking. We will accomplish these aims using Western blotting, fixed-cell, cell fractionation and live-cell
microscopy. These studies extend the fundamental molecular mechanisms of LPL regulation and identify new
targets for treating LPL deficiency during T2D.

## Key facts

- **NIH application ID:** 10020172
- **Project number:** 5F31DK122728-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Benjamin S Roberts
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $22,712
- **Award type:** 5
- **Project period:** 2019-12-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020172

## Citation

> US National Institutes of Health, RePORTER application 10020172, The Molecular Regulation of Lipoprotein Lipase Activity (5F31DK122728-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10020172. Licensed CC0.

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