Decreasing Phosphatidylcholine on the Surface of the Lipid Droplet Correlates with Altered Protein Binding and Steatosis.

Laura Listenberger,Elizabeth Brown,Natalia Osna,Elizabeth Townsend,Kusum Kharbanda,Mitchell Matis,Rebecca Sampathkumar,Cassandra Rickertsen,Anastasia Hains,Emily Inwards,Angela Stoeckman

doi:10.3390/cells7120230

Abstract

Alcoholic fatty liver disease (AFLD) is characterized by an abnormal accumulation of lipid droplets (LDs) in the liver. Here, we explore the composition of hepatic LDs in a rat model of AFLD. Five to seven weeks of alcohol consumption led to significant increases in hepatic triglyceride mass, along with increases in LD number and size. Additionally, hepatic LDs from rats with early alcoholic liver injury show a decreased ratio of surface phosphatidylcholine (PC) to phosphatidylethanolamine (PE). This occurred in parallel with an increase in the LD association of perilipin 2, a prominent LD protein. To determine if changes to the LD phospholipid composition contributed to differences in protein association with LDs, we constructed liposomes that modeled the LD PC:PE ratios in AFLD and control rats. Reducing the ratio of PC to PE increased the binding of perilipin 2 to liposomes in an in vitro experiment. Moreover, we decreased the ratio of LD PC:PE in NIH 3T3 and AML12 cells by culturing these cells in choline-deficient media. We again detected increased association of specific LD proteins, including perilipin 2. Taken together, our experiments suggest an important link between LD phospholipids, protein composition, and lipid accumulation.

Highlights

Fatty liver is an early and consistent morphological feature of alcohol-related liver injury, and with continued alcohol consumption, can progress to cirrhosis and liver failure [1,2]
Since up to 70% of the triglycerides packaged and secreted by hepatocytes in very-low-density lipoproteins (VLDLs) are derived via lipolysis of preformed triglyceride stores in
lipid droplets (LDs) [40,41,42], the approximate 50% reduction in lipolysis observed in this study is consistent with our previous report showing a decreased in vivo VLDL secretion rate in the ethanol-fed rats compared to control rats [43]

Summary

Introduction

Fatty liver is an early and consistent morphological feature of alcohol-related liver injury, and with continued alcohol consumption, can progress to cirrhosis and liver failure [1,2]. The magnitude of this problem is notable; alcohol-related liver cirrhosis was responsible for nearly 500,000 deaths worldwide in 2010 [3]. LDs are composed of a core of neutral lipids including triglycerides and cholesteryl esters. The neutral lipid core of an LD is shielded from the surrounding cytosol by a phospholipid monolayer consisting mostly of phosphatidylcholine (PC)

Objectives

Methods

Results

Conclusion