Alcohol withdrawal alleviates adipose tissue inflammation in patients with alcoholic liver disease

Authors

  • Cosmin S. Voican,

    1. INSERM U996, IPSIT, Clamart, France
    2. Univ Paris-Sud, Faculté de médecine Paris-Sud, Kremlin-Bicêtre, France
    3. AP-HP, Hôpital Antoine Béclère, Service d'hépato-gastroentérologie et nutrition, Clamart, France
    4. DHU Hépatinov, Clamart, France
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  • Micheline Njiké-Nakseu,

    1. AP-HP, Hôpital Antoine Béclère, Service d'hépato-gastroentérologie et nutrition, Clamart, France
    2. DHU Hépatinov, Clamart, France
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  • Hédia Boujedidi,

    1. INSERM U996, IPSIT, Clamart, France
    2. Univ Paris-Sud, Faculté de médecine Paris-Sud, Kremlin-Bicêtre, France
    3. DHU Hépatinov, Clamart, France
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  • Nadège Barri-Ova,

    1. Univ Paris-Sud, Faculté de médecine Paris-Sud, Kremlin-Bicêtre, France
    2. AP-HP, Hôpital Antoine Béclère, Service d'hépato-gastroentérologie et nutrition, Clamart, France
    3. DHU Hépatinov, Clamart, France
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  • Laurence Bouchet-Delbos,

    1. INSERM U996, IPSIT, Clamart, France
    2. Univ Paris-Sud, Faculté de médecine Paris-Sud, Kremlin-Bicêtre, France
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  • Hélène Agostini,

    1. AP-HP, Hôpital Bicêtre, Unité de recherche clinique Paris-Sud, Kremlin-Bicêtre, France
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  • Sophie Maitre,

    1. AP-HP, Hôpital Antoine Béclère, Service de radiologie, Clamart, France
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  • Sophie Prévot,

    1. Univ Paris-Sud, Faculté de médecine Paris-Sud, Kremlin-Bicêtre, France
    2. AP-HP, Hôpital Antoine Béclère, Service d'anatomie pathologique, Clamart, France
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  • Anne-Marie Cassard-Doulcier,

    1. INSERM U996, IPSIT, Clamart, France
    2. Univ Paris-Sud, Faculté de médecine Paris-Sud, Kremlin-Bicêtre, France
    3. AP-HP, Hôpital Antoine Béclère, Service d'hépato-gastroentérologie et nutrition, Clamart, France
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  • Sylvie Naveau,

    1. INSERM U996, IPSIT, Clamart, France
    2. Univ Paris-Sud, Faculté de médecine Paris-Sud, Kremlin-Bicêtre, France
    3. AP-HP, Hôpital Antoine Béclère, Service d'hépato-gastroentérologie et nutrition, Clamart, France
    4. DHU Hépatinov, Clamart, France
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  • Gabriel Perlemuter

    Corresponding author
    1. INSERM U996, IPSIT, Clamart, France
    2. Univ Paris-Sud, Faculté de médecine Paris-Sud, Kremlin-Bicêtre, France
    3. AP-HP, Hôpital Antoine Béclère, Service d'hépato-gastroentérologie et nutrition, Clamart, France
    4. DHU Hépatinov, Clamart, France
    • Correspondence

      Professor Gabriel Perlemuter

      Service d'Hépato-Gastroentérologie, Hôpital Antoine Béclère

      157 rue de la Porte de Trivaux, 92141 Clamart Cedex, France

      Tel: +33 1 45 37 43 72

      Fax: +33 1 40 94 06 56

      e-mail: gabriel.perlemuter@abc.aphp.fr

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Abstract

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 NCT00388323).

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