Myristic acid induces proteomic and secretomic changes associated with steatosis, cytoskeleton remodeling, endoplasmic reticulum stress, protein turnover and exosome release in HepG2 cells

Giulia Speziali, Laura Liesinger, Juergen Gindlhuber, Christina Leopold, Bettina Pucher, Jessica Brandi, Annalisa Castagna, Tamara Tomin, Petra Krenn, Gerhard G Thallinger, Oliviero Olivieri, Nicola Martinelli, Dagmar Kratky, Matthias Schittmayer, Ruth Birner-Gruenberger, Daniela Cecconi

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Myristic acid, the 14-carbon saturated fatty acid (C14:0), is associated to an increased cardiovascular disease risk. Since it is found in low concentration in cells, its specific properties have not been fully analyzed. The aim of this study was to explore the cell response to this fatty acid to help explaining clinical findings on the relationship between C14:0 and cardiovascular disease. The human liver HepG2 cell line was used to investigate the hepatic response to C14:0 in a combined proteomic and secretomic approach. A total of 47 intracellular and 32 secreted proteins were deregulated after treatments with different concentrations of C14:0. Data are available via ProteomeXchange (PXD007902). In addition, C14:0 treatment of primary murine hepatocytes confirmed that C14:0 induces lipid droplet accumulation and elevates perilipin-2 levels. Functional enrichment analysis revealed that C14:0 modulates lipid droplet formation and cytoskeleton organization, induce ER stress, changes in exosome and extracellular miRNA sorting in HepG2cells. Our data provide for the first time a proteomic profiling of the effects of C14:0 in human hepatoma cells and contribute to the elucidation of molecular mechanisms through which this fatty acid may cause adverse health effects.

BIOLOGICAL SIGNIFICANCE: Myristic acid is correlated with an increase in plasma cholesterol and mortality due to cardiovascular diseases. This study is the first example of an integration of proteomic and secretomic analysis of HepG2 cells to investigate the specific properties and functional roles of myristic acid on hepatic cells. Our analyses will lead to a better understanding of the myristic acid induced effects and can elicit new diagnostic and treatment strategies based on altered proteins.

LanguageEnglish
Pages118-130
JournalJournal of proteomics
Volume181
DOIs
StatusPublished - 15 Jun 2018

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Exosomes
Endoplasmic Reticulum Stress
Hep G2 Cells
Myristic Acid
Heat-Shock Proteins
Cytoskeleton
Proteomics
Cardiovascular Diseases
Fatty Acids
Hepatocytes
Lipids
Liver
MicroRNAs
Sorting
Hepatocellular Carcinoma
Proteins
Carbon
Cholesterol
Cells
Health

Fields of Expertise

  • Human- & Biotechnology
  • Information, Communication & Computing

Treatment code (Nähere Zuordnung)

  • Basic - Fundamental (Grundlagenforschung)

Cooperations

  • BioTechMed-Graz

Cite this

Myristic acid induces proteomic and secretomic changes associated with steatosis, cytoskeleton remodeling, endoplasmic reticulum stress, protein turnover and exosome release in HepG2 cells. / Speziali, Giulia; Liesinger, Laura; Gindlhuber, Juergen; Leopold, Christina; Pucher, Bettina; Brandi, Jessica; Castagna, Annalisa; Tomin, Tamara; Krenn, Petra; Thallinger, Gerhard G; Olivieri, Oliviero; Martinelli, Nicola; Kratky, Dagmar; Schittmayer, Matthias; Birner-Gruenberger, Ruth; Cecconi, Daniela.

In: Journal of proteomics, Vol. 181, 15.06.2018, p. 118-130.

Research output: Contribution to journalArticleResearchpeer-review

Speziali, G, Liesinger, L, Gindlhuber, J, Leopold, C, Pucher, B, Brandi, J, Castagna, A, Tomin, T, Krenn, P, Thallinger, GG, Olivieri, O, Martinelli, N, Kratky, D, Schittmayer, M, Birner-Gruenberger, R & Cecconi, D 2018, 'Myristic acid induces proteomic and secretomic changes associated with steatosis, cytoskeleton remodeling, endoplasmic reticulum stress, protein turnover and exosome release in HepG2 cells', Journal of proteomics, vol. 181, pp. 118-130. https://doi.org/10.1016/j.jprot.2018.04.008
Speziali, Giulia ; Liesinger, Laura ; Gindlhuber, Juergen ; Leopold, Christina ; Pucher, Bettina ; Brandi, Jessica ; Castagna, Annalisa ; Tomin, Tamara ; Krenn, Petra ; Thallinger, Gerhard G ; Olivieri, Oliviero ; Martinelli, Nicola ; Kratky, Dagmar ; Schittmayer, Matthias ; Birner-Gruenberger, Ruth ; Cecconi, Daniela. / Myristic acid induces proteomic and secretomic changes associated with steatosis, cytoskeleton remodeling, endoplasmic reticulum stress, protein turnover and exosome release in HepG2 cells. In: Journal of proteomics. 2018 ; Vol. 181. pp. 118-130.
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abstract = "Myristic acid, the 14-carbon saturated fatty acid (C14:0), is associated to an increased cardiovascular disease risk. Since it is found in low concentration in cells, its specific properties have not been fully analyzed. The aim of this study was to explore the cell response to this fatty acid to help explaining clinical findings on the relationship between C14:0 and cardiovascular disease. The human liver HepG2 cell line was used to investigate the hepatic response to C14:0 in a combined proteomic and secretomic approach. A total of 47 intracellular and 32 secreted proteins were deregulated after treatments with different concentrations of C14:0. Data are available via ProteomeXchange (PXD007902). In addition, C14:0 treatment of primary murine hepatocytes confirmed that C14:0 induces lipid droplet accumulation and elevates perilipin-2 levels. Functional enrichment analysis revealed that C14:0 modulates lipid droplet formation and cytoskeleton organization, induce ER stress, changes in exosome and extracellular miRNA sorting in HepG2cells. Our data provide for the first time a proteomic profiling of the effects of C14:0 in human hepatoma cells and contribute to the elucidation of molecular mechanisms through which this fatty acid may cause adverse health effects.BIOLOGICAL SIGNIFICANCE: Myristic acid is correlated with an increase in plasma cholesterol and mortality due to cardiovascular diseases. This study is the first example of an integration of proteomic and secretomic analysis of HepG2 cells to investigate the specific properties and functional roles of myristic acid on hepatic cells. Our analyses will lead to a better understanding of the myristic acid induced effects and can elicit new diagnostic and treatment strategies based on altered proteins.",
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T1 - Myristic acid induces proteomic and secretomic changes associated with steatosis, cytoskeleton remodeling, endoplasmic reticulum stress, protein turnover and exosome release in HepG2 cells

AU - Speziali, Giulia

AU - Liesinger, Laura

AU - Gindlhuber, Juergen

AU - Leopold, Christina

AU - Pucher, Bettina

AU - Brandi, Jessica

AU - Castagna, Annalisa

AU - Tomin, Tamara

AU - Krenn, Petra

AU - Thallinger, Gerhard G

AU - Olivieri, Oliviero

AU - Martinelli, Nicola

AU - Kratky, Dagmar

AU - Schittmayer, Matthias

AU - Birner-Gruenberger, Ruth

AU - Cecconi, Daniela

N1 - Copyright © 2018. Published by Elsevier B.V.

PY - 2018/6/15

Y1 - 2018/6/15

N2 - Myristic acid, the 14-carbon saturated fatty acid (C14:0), is associated to an increased cardiovascular disease risk. Since it is found in low concentration in cells, its specific properties have not been fully analyzed. The aim of this study was to explore the cell response to this fatty acid to help explaining clinical findings on the relationship between C14:0 and cardiovascular disease. The human liver HepG2 cell line was used to investigate the hepatic response to C14:0 in a combined proteomic and secretomic approach. A total of 47 intracellular and 32 secreted proteins were deregulated after treatments with different concentrations of C14:0. Data are available via ProteomeXchange (PXD007902). In addition, C14:0 treatment of primary murine hepatocytes confirmed that C14:0 induces lipid droplet accumulation and elevates perilipin-2 levels. Functional enrichment analysis revealed that C14:0 modulates lipid droplet formation and cytoskeleton organization, induce ER stress, changes in exosome and extracellular miRNA sorting in HepG2cells. Our data provide for the first time a proteomic profiling of the effects of C14:0 in human hepatoma cells and contribute to the elucidation of molecular mechanisms through which this fatty acid may cause adverse health effects.BIOLOGICAL SIGNIFICANCE: Myristic acid is correlated with an increase in plasma cholesterol and mortality due to cardiovascular diseases. This study is the first example of an integration of proteomic and secretomic analysis of HepG2 cells to investigate the specific properties and functional roles of myristic acid on hepatic cells. Our analyses will lead to a better understanding of the myristic acid induced effects and can elicit new diagnostic and treatment strategies based on altered proteins.

AB - Myristic acid, the 14-carbon saturated fatty acid (C14:0), is associated to an increased cardiovascular disease risk. Since it is found in low concentration in cells, its specific properties have not been fully analyzed. The aim of this study was to explore the cell response to this fatty acid to help explaining clinical findings on the relationship between C14:0 and cardiovascular disease. The human liver HepG2 cell line was used to investigate the hepatic response to C14:0 in a combined proteomic and secretomic approach. A total of 47 intracellular and 32 secreted proteins were deregulated after treatments with different concentrations of C14:0. Data are available via ProteomeXchange (PXD007902). In addition, C14:0 treatment of primary murine hepatocytes confirmed that C14:0 induces lipid droplet accumulation and elevates perilipin-2 levels. Functional enrichment analysis revealed that C14:0 modulates lipid droplet formation and cytoskeleton organization, induce ER stress, changes in exosome and extracellular miRNA sorting in HepG2cells. Our data provide for the first time a proteomic profiling of the effects of C14:0 in human hepatoma cells and contribute to the elucidation of molecular mechanisms through which this fatty acid may cause adverse health effects.BIOLOGICAL SIGNIFICANCE: Myristic acid is correlated with an increase in plasma cholesterol and mortality due to cardiovascular diseases. This study is the first example of an integration of proteomic and secretomic analysis of HepG2 cells to investigate the specific properties and functional roles of myristic acid on hepatic cells. Our analyses will lead to a better understanding of the myristic acid induced effects and can elicit new diagnostic and treatment strategies based on altered proteins.

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DO - 10.1016/j.jprot.2018.04.008

M3 - Article

VL - 181

SP - 118

EP - 130

JO - Journal of proteomics

T2 - Journal of proteomics

JF - Journal of proteomics

SN - 1874-3919

ER -