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Cited by 240Liver Disease Diagnosis and TreatmentAdipokines, Inflammation, and Metabolic DiseasesLiver physiology and pathology

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

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Bertola, Adeline, Bonnafous, Stéphanie, Anty, Rodolphe, Patouraux, Stéphanie, Saint-Paul, Marie-Christine, Iannelli, Antonio, Gugenheim, Jean, Barr, Jonathan +4 more·2010·PLoS ONE
DOI 10.1371/journal.pone.0013577PMC PMC2962651
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Abstract

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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  • Human studies have yielded conflicting results, with some reporting increased intrahepatic Treg numbers and others reduced frequencies in patients with MASLD.

    “Human studies have similarly yielded conflicting results, with some studies reporting increased intrahepatic Treg numbers, whereas others have observed reduced frequencies in patients with MASLD (Bertola et al. 2010; Dywicki et al. 2022; Wang et al. 2021c).”

    From The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion (2026) · cites this paper as Bertola et al. 2010

    The Introduction (page unavailable) mentions a possible reduction in regulatory T cells but does not report intrahepatic Treg numbers in patients. The Results and Discussion address hepatic gene expression and NKT cells, not conflicting human findings on intrahepatic Treg frequencies. Searches for Treg, FOXP3, and CD4/CD25 did not establish the attributed claim. (LLM, conf=0.76)

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Authors
Bertola, A., Bonnafous, S., Anty, R., Patouraux, S., Saint-Paul, M.-C., Iannelli, A., Gugenheim, J., Barr, J., Mato, J. M., Le Marchand-Brustel, Y., Tran, A., & Gual, P.
Affiliations
  • Inserm (FR)
  • Centre Hospitalier Universitaire de Nice (FR)
  • CIC bioGUNE (ES)
Corresponding author
Gual, Philippe
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-10-22
Volume
5
Issue
10
Pages
e13577
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0013577
PMC
PMC2962651
OpenAlex
W2011709384
Cited by
240
References
8
Citations by year
2026: 5 · 2025: 8 · 2024: 11 · 2023: 18 · 2022: 20 · 2021: 19 · 2020: 18 · 2019: 20 · 2018: 13 · 2017: 19 · 2016: 9 · 2015: 19 · 2014: 13 · 2013: 17 · 2012: 21
FWCI
11.20
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Association pour la Recherche sur le Cancer
  • European Commission (LSHM‐CT‐2005‐018734)
  • Agence Nationale de la Recherche (ANR-05-PCOD-0025, ANR-05)
  • Institut National de la Santé et de la Recherche Médicale
  • Association Française pour l'Etude du Foie
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
nonalcoholic steatohepatitis, obesity, hepatic gene expression, inflammatory genes, immune response genes, chemokines, chemokine receptors, Th1 cytokines, semaphorins, Toll-like receptor pathway, hepatic steatosis, palmitate, NAFLD pathogenesis, visceral adipose tissue
MeSH terms
Adult, Fatty Liver, Female, Humans, Inflammation, Liver, Male, Obesity, Morbid, Case-Control Studies, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Non-alcoholic Fatty Liver Disease

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