# Role of lipid droplet protein in obesity and diabetes

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $361,233

## Abstract

Lipids within cells are stored in an organelle termed lipid droplets (LDs) that consist of neutral lipids core of
diacylglycerides, triglycerides, and cholesterol ester covered by a single layer of phospholipids. Recent
evidence indicates a pivotal role of LD in the spatial and temporal regulation of intracellular lipid metabolism.
Our project aims to understand the regulation of intracellular lipid metabolism through the study of LD in
beta cells considering the critical role of lipids in beta cell. Metabolites produced by lipolysis augment insulin
secretion, while unregulated accumulation of lipids impair beta cell health and leads to diabetes. The
perilipin (PLIN1-5) family of proteins resides on the surface of LD and plays a key role in the formation and
mobilization of LD. Our goal is to understand the mechanisms by which PLIN affects insulin secretion and to
clarify the role of PLIN in the pathogenesis of abnormal lipid metabolism in beta cells under type 2 diabetes
(T2D). We have demonstrated that both PLIN2 and PLIN5 are expressed in human and mouse islets, but
their expression is differentially regulated. We have shown that PLIN5 plays a significant role in increasing
insulin secretion likely through the regulation of lipid metabolism acutely, especially lipolysis in beta cells.
PLIN2 may aid adaptation of beta cells to nutritional stress. Thus, we hypothesize that PLIN2 and 5, each
with unique molecular characteristics coordinately achieve the efficient regulation of insulin secretion and
protect beta cells under nutritional stress. The hypothesis will be tested by 2 aims.
Specific Aim 1: Determine the mechanism by which PLIN5 augments GSIS and lipolysis. PLIN5 augments
GSIS both in vitro and in vivo, which we hypothesize is mediated by lipolysis. Here, we will delineate the
pathway connecting PLIN5 and GSIS. The impact of PLIN5 deficiency in beta cells on glucose homeostasis
will be tested in beta cell specific PLIN5 knockout mice. The contribution of PLIN5 phosphorylation in lipid
metabolism and GSIS will be tested using phosphorylation resistant mutant PLIN5 expressed in cultured
cell and in beta cells of mice. Lastly, the molecular target that mediates the augmentation of PLIN5 will be
determined by increase lipolysis through mutant PLIN5 and pharmacological modulation of lipolysis.
Specific Aim 2: Determine how perilipins protect beta cells under nutritional stress. Studies in yeast,
drosophila, and mouse liver implicate that LDs protect cells under nutritional stress. In beta cells, PLIN2 is
highly expressed and increased by fatty acids. We have obtained preliminary data that the loss of PLIN2 in
beta cells impair GSIS and islet adaptation to high fat feeding. We will determine the mechanism by which
PLIN2 protect beta cells under nutritional stress. Also, we will analyze how islet PLINs and lipidome are
altered in human islets affected by T2D.
Our study holds promise to identify a new target that supports GSIS and protects beta c...

## Key facts

- **NIH application ID:** 9900782
- **Project number:** 5R01DK090490-10
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Yumi Imai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $361,233
- **Award type:** 5
- **Project period:** 2011-02-15 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900782

## Citation

> US National Institutes of Health, RePORTER application 9900782, Role of lipid droplet protein in obesity and diabetes (5R01DK090490-10). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9900782. Licensed CC0.

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