Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury
UMass Chan AffiliationsUMass Metabolic Network
Graduate School of Biomedical Sciences
Department of Medicine, Division of Gastroenterology
Document TypeJournal Article
KeywordsCellular and Molecular Physiology
Digestive System Diseases
Reproductive and Urinary Physiology
Substance Abuse and Addiction
MetadataShow full item record
AbstractAlcoholic 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 TNFalpha, 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.
SourcePLoS One. 2016 Oct 6;11(10):e0164225. doi: 10.1371/journal.pone.0164225. eCollection 2016. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40164
Related ResourcesLink to Article in PubMed
RightsCopyright: © 2016 Fulham, Mandrekar.
Except where otherwise noted, this item's license is described as Copyright: © 2016 Fulham, Mandrekar.