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

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...

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Main Authors: Laura Listenberger, Elizabeth Townsend, Cassandra Rickertsen, Anastasia Hains, Elizabeth Brown, Emily G. Inwards, Angela K. Stoeckman, Mitchell P. Matis, Rebecca S. Sampathkumar, Natalia A. Osna, Kusum K. Kharbanda
Format: Article
Language:English
Published: MDPI AG 2018-11-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/7/12/230
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author Laura Listenberger
Elizabeth Townsend
Cassandra Rickertsen
Anastasia Hains
Elizabeth Brown
Emily G. Inwards
Angela K. Stoeckman
Mitchell P. Matis
Rebecca S. Sampathkumar
Natalia A. Osna
Kusum K. Kharbanda
author_facet Laura Listenberger
Elizabeth Townsend
Cassandra Rickertsen
Anastasia Hains
Elizabeth Brown
Emily G. Inwards
Angela K. Stoeckman
Mitchell P. Matis
Rebecca S. Sampathkumar
Natalia A. Osna
Kusum K. Kharbanda
author_sort Laura Listenberger
collection DOAJ
description 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.
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spelling doaj.art-398711a161bc4946983942c65349ea352023-09-03T03:46:28ZengMDPI AGCells2073-44092018-11-0171223010.3390/cells7120230cells7120230Decreasing Phosphatidylcholine on the Surface of the Lipid Droplet Correlates with Altered Protein Binding and SteatosisLaura Listenberger0Elizabeth Townsend1Cassandra Rickertsen2Anastasia Hains3Elizabeth Brown4Emily G. Inwards5Angela K. Stoeckman6Mitchell P. Matis7Rebecca S. Sampathkumar8Natalia A. Osna9Kusum K. Kharbanda10Departments of Biology and Chemistry, St. Olaf College, Northfield, MN 55057, USADepartments of Biology and Chemistry, St. Olaf College, Northfield, MN 55057, USADepartments of Biology and Chemistry, St. Olaf College, Northfield, MN 55057, USADepartments of Biology and Chemistry, St. Olaf College, Northfield, MN 55057, USADepartments of Biology and Chemistry, St. Olaf College, Northfield, MN 55057, USADepartment of Chemistry, Bethel University, St. Paul, MN 55112, USADepartment of Chemistry, Bethel University, St. Paul, MN 55112, USAResearch Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE and Departments of Internal Medicine and Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68105, USAResearch Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE and Departments of Internal Medicine and Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68105, USAResearch Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE and Departments of Internal Medicine and Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68105, USAResearch Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE and Departments of Internal Medicine and Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68105, USAAlcoholic 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.https://www.mdpi.com/2073-4409/7/12/230lipid dropletsperilipinsphosphatidylcholinephosphatidylethanolaminesteatohepatitis
spellingShingle Laura Listenberger
Elizabeth Townsend
Cassandra Rickertsen
Anastasia Hains
Elizabeth Brown
Emily G. Inwards
Angela K. Stoeckman
Mitchell P. Matis
Rebecca S. Sampathkumar
Natalia A. Osna
Kusum K. Kharbanda
Decreasing Phosphatidylcholine on the Surface of the Lipid Droplet Correlates with Altered Protein Binding and Steatosis
Cells
lipid droplets
perilipins
phosphatidylcholine
phosphatidylethanolamine
steatohepatitis
title Decreasing Phosphatidylcholine on the Surface of the Lipid Droplet Correlates with Altered Protein Binding and Steatosis
title_full Decreasing Phosphatidylcholine on the Surface of the Lipid Droplet Correlates with Altered Protein Binding and Steatosis
title_fullStr Decreasing Phosphatidylcholine on the Surface of the Lipid Droplet Correlates with Altered Protein Binding and Steatosis
title_full_unstemmed Decreasing Phosphatidylcholine on the Surface of the Lipid Droplet Correlates with Altered Protein Binding and Steatosis
title_short Decreasing Phosphatidylcholine on the Surface of the Lipid Droplet Correlates with Altered Protein Binding and Steatosis
title_sort decreasing phosphatidylcholine on the surface of the lipid droplet correlates with altered protein binding and steatosis
topic lipid droplets
perilipins
phosphatidylcholine
phosphatidylethanolamine
steatohepatitis
url https://www.mdpi.com/2073-4409/7/12/230
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