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Hepatic Expression Patterns of Inflammatory and Immune Response Genes Associated with Obesity and NASH in Morbidly Obese Patients

BACKGROUND: Obesity modulates inflammation and activation of immune pathways which can lead to liver complications. We aimed at identifying expression patterns of inflammatory and immune response genes specifically associated with obesity and NASH in the liver of morbidly obese patients. METHODOLOGY...

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Autores principales: Bertola, Adeline, Bonnafous, Stéphanie, Anty, Rodolphe, Patouraux, Stéphanie, Saint-Paul, Marie-Christine, Iannelli, Antonio, Gugenheim, Jean, Barr, Jonathan, Mato, José M., Le Marchand-Brustel, Yannick, Tran, Albert, Gual, Philippe
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2962651/
https://www.ncbi.nlm.nih.gov/pubmed/21042596
http://dx.doi.org/10.1371/journal.pone.0013577
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author Bertola, Adeline
Bonnafous, Stéphanie
Anty, Rodolphe
Patouraux, Stéphanie
Saint-Paul, Marie-Christine
Iannelli, Antonio
Gugenheim, Jean
Barr, Jonathan
Mato, José M.
Le Marchand-Brustel, Yannick
Tran, Albert
Gual, Philippe
author_facet Bertola, Adeline
Bonnafous, Stéphanie
Anty, Rodolphe
Patouraux, Stéphanie
Saint-Paul, Marie-Christine
Iannelli, Antonio
Gugenheim, Jean
Barr, Jonathan
Mato, José M.
Le Marchand-Brustel, Yannick
Tran, Albert
Gual, Philippe
author_sort Bertola, Adeline
collection PubMed
description BACKGROUND: Obesity modulates inflammation and activation of immune pathways which can lead to liver complications. We aimed at identifying expression patterns of inflammatory and immune response genes specifically associated with obesity and NASH in the liver of morbidly obese patients. METHODOLOGY/PRINCIPAL FINDINGS: Expression of 222 genes was evaluated by quantitative RT-PCR in the liver of morbidly obese patients with histologically normal liver (n = 6), or with severe steatosis without (n = 6) or with NASH (n = 6), and in lean controls (n = 5). Hepatic expression of 58 out of 222 inflammatory and immune response genes was upregulated in NASH patients. The most notable changes occurred in genes encoding chemokines and chemokine receptors involved in leukocyte recruitment, CD and cytokines involved in the T cell activation towards a Th1 phenotype, and immune semaphorins. This regulation seems to be specific for the liver since visceral adipose tissue expression and serum levels of MCP1, IP10, TNFα and IL6 were not modified. Importantly, 47 other genes were already upregulated in histologically normal liver (e.g. CRP, Toll-like receptor (TLR) pathway). Interestingly, serum palmitate, known to activate the TLR pathway, was increased with steatosis. CONCLUSION/SIGNIFICANCE: The liver of obese patients without histological abnormalities already displayed a low-grade inflammation and could be more responsive to activators of the TLR pathway. NASH was then characterized by a specific gene signature. These findings help to identify new potential actors of the pathogenesis of NAFLD.
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spelling pubmed-29626512010-11-01 Hepatic Expression Patterns of Inflammatory and Immune Response Genes Associated with Obesity and NASH in Morbidly Obese Patients Bertola, Adeline Bonnafous, Stéphanie Anty, Rodolphe Patouraux, Stéphanie Saint-Paul, Marie-Christine Iannelli, Antonio Gugenheim, Jean Barr, Jonathan Mato, José M. Le Marchand-Brustel, Yannick Tran, Albert Gual, Philippe PLoS One Research Article BACKGROUND: Obesity modulates inflammation and activation of immune pathways which can lead to liver complications. We aimed at identifying expression patterns of inflammatory and immune response genes specifically associated with obesity and NASH in the liver of morbidly obese patients. METHODOLOGY/PRINCIPAL FINDINGS: Expression of 222 genes was evaluated by quantitative RT-PCR in the liver of morbidly obese patients with histologically normal liver (n = 6), or with severe steatosis without (n = 6) or with NASH (n = 6), and in lean controls (n = 5). Hepatic expression of 58 out of 222 inflammatory and immune response genes was upregulated in NASH patients. The most notable changes occurred in genes encoding chemokines and chemokine receptors involved in leukocyte recruitment, CD and cytokines involved in the T cell activation towards a Th1 phenotype, and immune semaphorins. This regulation seems to be specific for the liver since visceral adipose tissue expression and serum levels of MCP1, IP10, TNFα and IL6 were not modified. Importantly, 47 other genes were already upregulated in histologically normal liver (e.g. CRP, Toll-like receptor (TLR) pathway). Interestingly, serum palmitate, known to activate the TLR pathway, was increased with steatosis. CONCLUSION/SIGNIFICANCE: The liver of obese patients without histological abnormalities already displayed a low-grade inflammation and could be more responsive to activators of the TLR pathway. NASH was then characterized by a specific gene signature. These findings help to identify new potential actors of the pathogenesis of NAFLD. Public Library of Science 2010-10-22 /pmc/articles/PMC2962651/ /pubmed/21042596 http://dx.doi.org/10.1371/journal.pone.0013577 Text en Bertola et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bertola, Adeline
Bonnafous, Stéphanie
Anty, Rodolphe
Patouraux, Stéphanie
Saint-Paul, Marie-Christine
Iannelli, Antonio
Gugenheim, Jean
Barr, Jonathan
Mato, José M.
Le Marchand-Brustel, Yannick
Tran, Albert
Gual, Philippe
Hepatic Expression Patterns of Inflammatory and Immune Response Genes Associated with Obesity and NASH in Morbidly Obese Patients
title Hepatic Expression Patterns of Inflammatory and Immune Response Genes Associated with Obesity and NASH in Morbidly Obese Patients
title_full Hepatic Expression Patterns of Inflammatory and Immune Response Genes Associated with Obesity and NASH in Morbidly Obese Patients
title_fullStr Hepatic Expression Patterns of Inflammatory and Immune Response Genes Associated with Obesity and NASH in Morbidly Obese Patients
title_full_unstemmed Hepatic Expression Patterns of Inflammatory and Immune Response Genes Associated with Obesity and NASH in Morbidly Obese Patients
title_short Hepatic Expression Patterns of Inflammatory and Immune Response Genes Associated with Obesity and NASH in Morbidly Obese Patients
title_sort hepatic expression patterns of inflammatory and immune response genes associated with obesity and nash in morbidly obese patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2962651/
https://www.ncbi.nlm.nih.gov/pubmed/21042596
http://dx.doi.org/10.1371/journal.pone.0013577
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