Premium
Alcohol withdrawal alleviates adipose tissue inflammation in patients with alcoholic liver disease
Author(s) -
Voican Cosmin S.,
NjikéNakseu Micheline,
Boujedidi Hédia,
BarriOva Nadège,
BouchetDelbos Laurence,
Agostini Hélène,
Maitre Sophie,
Prévot Sophie,
CassardDoulcier AnneMarie,
Naveau Sylvie,
Perlemuter Gabriel
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12575
Subject(s) - adipose tissue , alcoholic liver disease , steatosis , inflammation , adipokine , medicine , liver injury , chemokine , fatty liver , inflammasome , liver disease , endocrinology , immunology , pathology , cirrhosis , insulin resistance , insulin , disease
Background & Aims Patients with alcoholic liver disease ( ALD ) display inflammation of the subcutaneous adipose tissue ( SAT ) which correlates with liver lesions. We examined macrophage markers and polarization in the SAT of alcoholic patients and adipokine expression according to liver inflammation; we studied the consequences of alcohol withdrawal. Patients and methods Forty‐seven patients with ALD were prospectively included. SAT and blood samples were collected at inclusion and after 1 week of alcohol withdrawal. Pro‐inflammatory cytokines/chemokines, inflammasome components and products, adipokine expression levels, macrophage markers and polarization in liver and SAT samples were assessed by RT ‐ PCR arrays. Results mRNA expression level of chemokines (IL8, semaphorin 7A) correlated with hepatic steatosis in both liver and SAT. Liver expression of inflammasome components (IL1β, IL18, caspase‐1) and SAT IL6 and CCL2 correlated with liver damage. In patients with mild ALD, 1 week of alcohol withdrawal was sufficient to decrease expression level of total macrophage markers in the adipose tissue, to orient adipose tissue macrophages (ATM) towards an anti‐inflammatory M2 phenotype and to decrease the mRNA expression of cytokines/chemokines (IL18, CCL2, osteopontin, semaphorin 7A). In patients with severe ALD, 1 week of abstinence was also associated with an increase in CCL18 expression. Conclusions In alcoholic patients, upregulation of chemotactic factors in the liver and SAT is an early event that begins as early as the steatosis stage. The inflammasome pathway is upregulated in the liver of patients with ALD . One week of alcohol withdrawal alleviates macrophage infiltration in SAT and orients ATM towards a M2 anti‐inflammatory phenotype; this implicates alcohol in adipose tissue inflammation (ClinicalTrials.gov NCT 00388323).