# Kansas Center for Metabolism and Obesity REsearch (KC-MORE) - Project 4

> **NIH NIH P20** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $290,599

## Abstract

PROJECT 4 (NI): PROJECT SUMMARY
Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent form of liver disease associated with obesity,
diabetes and other metabolic diseases. The molecular basis of the development of NAFLD and obesity are still
poorly understood. As a result, no effective therapeutic treatments for this burgeoning health problem are
available. Thus, there is a clear unmet research need in this area. Liver can modulate the processes of NAFLD
and other metabolic comorbidities including obesity by secreting hepatokines. Adropin is one of the hepatokines
involved in glucose and lipid metabolism, energy homeostasis, insulin sensitivity and NAFLD. Hepatic very-low-
density lipoprotein (VLDL) secretion is essential in regulating intrahepatic and intravascular lipid homeostasis,
and impaired VLDL secretion leads to steatosis. Vacuole membrane protein 1 (VMP1) is an ER membrane
protein that regulates autophagy by promoting the closure of autophagosomes. Recent evidence demonstrates
that VMP1 plays a critical role in lipoprotein secretion independent of its autophagy function in cultured hepatoma
cells and zebrafish. However, the mechanisms by which VMP1 regulates lipid metabolism, adropin or other
hepatokine secretion and obesity are unclear. The major OBJECTIVES of this application are to investigate
novel mechanisms by which VMP1 regulates VLDL and adropin secretion as well as the liver-adipose crosstalk
in the pathogenesis of NAFLD and its impact on obesity. Our proposal is SIGNIFICANT because it is to
investigate a novel pathway in regulating lipid metabolism and adropin secretion which regulate the development
of NAFLD and obesity. Work performed under this application will enrich the field regarding the critical role of
VMP1 as a central regulator which regulate VLDL and adropin secretion in the development of NAFLD and
obesity. Our overall SCIENTIFIC PREMISE is that elucidating pathways whereby VMP1 improves VLDL and
adropin secretion and protects NAFLD and obesity. Our proposal is supported by KEY PRELIMINARY DATA
including: 1) Hepatocyte-specific deletion of VMP1 in mice impaired VLDL secretion resulting in hepatic
steatosis; 2) Loss of hepatic VMP1 severely impaired VLDL secretion associated with markedly decreased COPII
complex proteins; 3) Overexpression of VMP1 in mouse livers protected high fat diet (HFD)–induced liver
steatosis, hyperlipidemia and obesity, which was associated with increased serum adropin levels. Two
SPECIFIC AIMS are proposed: 1) Determine the mechanisms by which loss of VMP1 decreases COPII and
ERGIC-53 that impairs adropin ER-Golgi trafficking and secretion; 2) Determine the role of VMP1 in mediating
adropin secretion and regulating liver-adipose crosstalk in NAFLD and obesity. The LONGTERM GOAL of this
work is to identify VMP1-dependent pathways in the pathogenesis of NAFLD and obesity and develop potential
strategies for prevention and treatment of NAFLD and obesity by improving VMP1-mediated VLD...

## Key facts

- **NIH application ID:** 10335444
- **Project number:** 1P20GM144269-01
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Hongmin Ni
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $290,599
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335444

## Citation

> US National Institutes of Health, RePORTER application 10335444, Kansas Center for Metabolism and Obesity REsearch (KC-MORE) - Project 4 (1P20GM144269-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10335444. Licensed CC0.

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