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Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury

Alcoholic liver disease occurs due to chronic, heavy drinking and is driven both by metabolic alterations and immune cell activation. Women are at a higher risk than men for developing alcohol induced liver injury and this dimorphism is reflected in animal models of alcoholic liver disease. The impo...

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Autores principales: Fulham, Melissa A., Mandrekar, Pranoti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053524/
https://www.ncbi.nlm.nih.gov/pubmed/27711160
http://dx.doi.org/10.1371/journal.pone.0164225
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author Fulham, Melissa A.
Mandrekar, Pranoti
author_facet Fulham, Melissa A.
Mandrekar, Pranoti
author_sort Fulham, Melissa A.
collection PubMed
description Alcoholic liver disease occurs due to chronic, heavy drinking and is driven both by metabolic alterations and immune cell activation. Women are at a higher risk than men for developing alcohol induced liver injury and this dimorphism is reflected in animal models of alcoholic liver disease. The importance of adipose tissue in alcoholic liver disease is emerging. Chronic alcohol consumption causes adipose tissue inflammation, which can influence liver injury. Sex differences in body fat composition are well known. However, it is still unclear if alcohol-induced adipose tissue inflammation occurs in a sex-dependent manner. Here we have employed the clinically relevant NIAAA model of chronic-binge alcohol consumption to investigate this sexual dimorphism. We report that female mice have greater liver injury than male mice despite lower alcohol consumption. Chronic-binge alcohol induces adipose tissue inflammation in vivo in female mice, which is illustrated by increased expression of TNFα, IL-6, and CCL2, compared to only IL-6 induction in male adipose tissue. Further, macrophage activation markers such as CD68 as well as the pro-inflammatory activation markers CD11b and CD11c were higher in female adipose tissue. Interestingly, alcohol induced expression of TLR2, 3, 4, and 9 in female but not male adipose tissue, without affecting the TLR adaptor, MyD88. Higher trends of serum endotoxin in female mice may likely contribute to adipose tissue inflammation. In vitro chronic alcohol-mediated sensitization of macrophages to endotoxin is independent of sex. In summary, we demonstrate for the first time that there is a sexual dimorphism in alcohol-induced adipose tissue inflammation and female mice exhibit a higher degree of inflammation than male mice.
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spelling pubmed-50535242016-10-27 Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury Fulham, Melissa A. Mandrekar, Pranoti PLoS One Research Article Alcoholic liver disease occurs due to chronic, heavy drinking and is driven both by metabolic alterations and immune cell activation. Women are at a higher risk than men for developing alcohol induced liver injury and this dimorphism is reflected in animal models of alcoholic liver disease. The importance of adipose tissue in alcoholic liver disease is emerging. Chronic alcohol consumption causes adipose tissue inflammation, which can influence liver injury. Sex differences in body fat composition are well known. However, it is still unclear if alcohol-induced adipose tissue inflammation occurs in a sex-dependent manner. Here we have employed the clinically relevant NIAAA model of chronic-binge alcohol consumption to investigate this sexual dimorphism. We report that female mice have greater liver injury than male mice despite lower alcohol consumption. Chronic-binge alcohol induces adipose tissue inflammation in vivo in female mice, which is illustrated by increased expression of TNFα, IL-6, and CCL2, compared to only IL-6 induction in male adipose tissue. Further, macrophage activation markers such as CD68 as well as the pro-inflammatory activation markers CD11b and CD11c were higher in female adipose tissue. Interestingly, alcohol induced expression of TLR2, 3, 4, and 9 in female but not male adipose tissue, without affecting the TLR adaptor, MyD88. Higher trends of serum endotoxin in female mice may likely contribute to adipose tissue inflammation. In vitro chronic alcohol-mediated sensitization of macrophages to endotoxin is independent of sex. In summary, we demonstrate for the first time that there is a sexual dimorphism in alcohol-induced adipose tissue inflammation and female mice exhibit a higher degree of inflammation than male mice. Public Library of Science 2016-10-06 /pmc/articles/PMC5053524/ /pubmed/27711160 http://dx.doi.org/10.1371/journal.pone.0164225 Text en © 2016 Fulham, Mandrekar http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Fulham, Melissa A.
Mandrekar, Pranoti
Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury
title Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury
title_full Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury
title_fullStr Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury
title_full_unstemmed Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury
title_short Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury
title_sort sexual dimorphism in alcohol induced adipose inflammation relates to liver injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053524/
https://www.ncbi.nlm.nih.gov/pubmed/27711160
http://dx.doi.org/10.1371/journal.pone.0164225
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