Incorporation of exogenous lipids modulates insulin signaling in the hepatoma cell line, HepG2

Emmanuelle Meuillet, Valérie Leray, Pierre Hubert, Claude Leray, Gérard Cremel

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The lipid content of cultured cells can be experimentally modified by supplementing the culture medium with specific lipids or by the use of phospholipases. In the case of the insulin receptor, these methods have contributed to a better understanding of lipid disorder-related diseases. Previously, our laboratory demonstrated that experimental modification of the cellular lipid composition of an insulin-sensitive rat hepatoma cell line (ZHC) resulted in an alteration in insulin receptor binding and biological action (Bruneau et al., Biochim. Biophys. Acta 928 (1987) 287-296/297-304). In this paper, we have examined the effects of lipid modification in another hepatoma cell line, HepG2. Exogenous linoleic acid (LA, n-6), eicosapentaenoic acid (EPA, n-3) or hemisuccinate of cholesterol (CHS) was added to HepG2 cells, to create a cellular model in which membrane composition was modified. In this model, we have shown that: (1) lipids were incorporated in treated HepG2 cells, but redistributed differently when compared to treated ZHC cells; (2) that insulin signaling events, such as insulin receptor autophosphorylation and the phosphorylation of the major insulin receptor substrate (IRS-1) were altered in response to the addition of membrane lipids or cholesterol derived components; and (3) different lipids affected insulin receptor signaling differently. We have also shown that the loss of insulin receptor autophosphorylation in CHS-treated cells can be correlated with a decreased sensitivity to insulin. Overall, the results suggest that the lipid environment of the insulin receptor may play an important role in insulin signal transduction. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)38-48
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1454
Issue number1
DOIs
StatePublished - May 31 1999
Externally publishedYes

Fingerprint

Hepatocellular Carcinoma
Insulin Receptor
Insulin
Lipids
Cell Line
Hep G2 Cells
Cholesterol
Insulin Receptor Substrate Proteins
Eicosapentaenoic Acid
Phospholipases
Linoleic Acid
Membrane Lipids
Culture Media
Insulin Resistance
Cultured Cells
Signal Transduction
Phosphorylation
Membranes

Keywords

  • Cholesterol
  • Hepatoma cell
  • Insulin receptor
  • Lipid
  • Membrane

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

Cite this

Incorporation of exogenous lipids modulates insulin signaling in the hepatoma cell line, HepG2. / Meuillet, Emmanuelle; Leray, Valérie; Hubert, Pierre; Leray, Claude; Cremel, Gérard.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1454, No. 1, 31.05.1999, p. 38-48.

Research output: Contribution to journalArticle

Meuillet, Emmanuelle ; Leray, Valérie ; Hubert, Pierre ; Leray, Claude ; Cremel, Gérard. / Incorporation of exogenous lipids modulates insulin signaling in the hepatoma cell line, HepG2. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 1999 ; Vol. 1454, No. 1. pp. 38-48.
@article{69773895fa14424c8354a7639bb83dda,
title = "Incorporation of exogenous lipids modulates insulin signaling in the hepatoma cell line, HepG2",
abstract = "The lipid content of cultured cells can be experimentally modified by supplementing the culture medium with specific lipids or by the use of phospholipases. In the case of the insulin receptor, these methods have contributed to a better understanding of lipid disorder-related diseases. Previously, our laboratory demonstrated that experimental modification of the cellular lipid composition of an insulin-sensitive rat hepatoma cell line (ZHC) resulted in an alteration in insulin receptor binding and biological action (Bruneau et al., Biochim. Biophys. Acta 928 (1987) 287-296/297-304). In this paper, we have examined the effects of lipid modification in another hepatoma cell line, HepG2. Exogenous linoleic acid (LA, n-6), eicosapentaenoic acid (EPA, n-3) or hemisuccinate of cholesterol (CHS) was added to HepG2 cells, to create a cellular model in which membrane composition was modified. In this model, we have shown that: (1) lipids were incorporated in treated HepG2 cells, but redistributed differently when compared to treated ZHC cells; (2) that insulin signaling events, such as insulin receptor autophosphorylation and the phosphorylation of the major insulin receptor substrate (IRS-1) were altered in response to the addition of membrane lipids or cholesterol derived components; and (3) different lipids affected insulin receptor signaling differently. We have also shown that the loss of insulin receptor autophosphorylation in CHS-treated cells can be correlated with a decreased sensitivity to insulin. Overall, the results suggest that the lipid environment of the insulin receptor may play an important role in insulin signal transduction. Copyright (C) 1999 Elsevier Science B.V.",
keywords = "Cholesterol, Hepatoma cell, Insulin receptor, Lipid, Membrane",
author = "Emmanuelle Meuillet and Val{\'e}rie Leray and Pierre Hubert and Claude Leray and G{\'e}rard Cremel",
year = "1999",
month = "5",
day = "31",
doi = "10.1016/S0925-4439(99)00023-X",
language = "English (US)",
volume = "1454",
pages = "38--48",
journal = "Biochimica et Biophysica Acta - Molecular Basis of Disease",
issn = "0925-4439",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Incorporation of exogenous lipids modulates insulin signaling in the hepatoma cell line, HepG2

AU - Meuillet, Emmanuelle

AU - Leray, Valérie

AU - Hubert, Pierre

AU - Leray, Claude

AU - Cremel, Gérard

PY - 1999/5/31

Y1 - 1999/5/31

N2 - The lipid content of cultured cells can be experimentally modified by supplementing the culture medium with specific lipids or by the use of phospholipases. In the case of the insulin receptor, these methods have contributed to a better understanding of lipid disorder-related diseases. Previously, our laboratory demonstrated that experimental modification of the cellular lipid composition of an insulin-sensitive rat hepatoma cell line (ZHC) resulted in an alteration in insulin receptor binding and biological action (Bruneau et al., Biochim. Biophys. Acta 928 (1987) 287-296/297-304). In this paper, we have examined the effects of lipid modification in another hepatoma cell line, HepG2. Exogenous linoleic acid (LA, n-6), eicosapentaenoic acid (EPA, n-3) or hemisuccinate of cholesterol (CHS) was added to HepG2 cells, to create a cellular model in which membrane composition was modified. In this model, we have shown that: (1) lipids were incorporated in treated HepG2 cells, but redistributed differently when compared to treated ZHC cells; (2) that insulin signaling events, such as insulin receptor autophosphorylation and the phosphorylation of the major insulin receptor substrate (IRS-1) were altered in response to the addition of membrane lipids or cholesterol derived components; and (3) different lipids affected insulin receptor signaling differently. We have also shown that the loss of insulin receptor autophosphorylation in CHS-treated cells can be correlated with a decreased sensitivity to insulin. Overall, the results suggest that the lipid environment of the insulin receptor may play an important role in insulin signal transduction. Copyright (C) 1999 Elsevier Science B.V.

AB - The lipid content of cultured cells can be experimentally modified by supplementing the culture medium with specific lipids or by the use of phospholipases. In the case of the insulin receptor, these methods have contributed to a better understanding of lipid disorder-related diseases. Previously, our laboratory demonstrated that experimental modification of the cellular lipid composition of an insulin-sensitive rat hepatoma cell line (ZHC) resulted in an alteration in insulin receptor binding and biological action (Bruneau et al., Biochim. Biophys. Acta 928 (1987) 287-296/297-304). In this paper, we have examined the effects of lipid modification in another hepatoma cell line, HepG2. Exogenous linoleic acid (LA, n-6), eicosapentaenoic acid (EPA, n-3) or hemisuccinate of cholesterol (CHS) was added to HepG2 cells, to create a cellular model in which membrane composition was modified. In this model, we have shown that: (1) lipids were incorporated in treated HepG2 cells, but redistributed differently when compared to treated ZHC cells; (2) that insulin signaling events, such as insulin receptor autophosphorylation and the phosphorylation of the major insulin receptor substrate (IRS-1) were altered in response to the addition of membrane lipids or cholesterol derived components; and (3) different lipids affected insulin receptor signaling differently. We have also shown that the loss of insulin receptor autophosphorylation in CHS-treated cells can be correlated with a decreased sensitivity to insulin. Overall, the results suggest that the lipid environment of the insulin receptor may play an important role in insulin signal transduction. Copyright (C) 1999 Elsevier Science B.V.

KW - Cholesterol

KW - Hepatoma cell

KW - Insulin receptor

KW - Lipid

KW - Membrane

UR - http://www.scopus.com/inward/record.url?scp=0032964210&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032964210&partnerID=8YFLogxK

U2 - 10.1016/S0925-4439(99)00023-X

DO - 10.1016/S0925-4439(99)00023-X

M3 - Article

VL - 1454

SP - 38

EP - 48

JO - Biochimica et Biophysica Acta - Molecular Basis of Disease

JF - Biochimica et Biophysica Acta - Molecular Basis of Disease

SN - 0925-4439

IS - 1

ER -