Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury.
Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury.
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DOI：
10.1371/journal.pone.0164225
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Mandrekar P
中科院分区：
文献类型：
--
作者：
Fulham MA;Mandrekar P
酒精性肝病的发生是由于慢性、大量饮酒，并由代谢改变和免疫细胞激活驱动。女性发生酒精性肝损伤的风险高于男性，这种二态性在酒精性肝病的动物模型中得到了反映。脂肪组织在酒精性肝病中的重要性正在显现。长期饮酒会引起脂肪组织炎症，从而影响肝损伤。身体脂肪组成的性别差异是众所周知的。然而，目前尚不清楚酒精诱导的脂肪组织炎症是否以性别依赖的方式发生。在这里，我们采用临床相关的NIAAA慢性酗酒模型来研究这种两性异形。我们报告说，尽管雌性小鼠的酒精摄入量较低，但雌性小鼠的肝损伤比雄性小鼠更严重。慢性狂饮酒精在雌性小鼠体内诱导脂肪组织炎症，这可以通过TNFα、IL-6和CCL2的表达增加来证明，而在雄性脂肪组织中仅诱导IL-6。此外，巨噬细胞激活标志物如CD68以及促炎激活标志物CD11b和CD11c在女性脂肪组织中更高。有趣的是，酒精在女性脂肪组织中诱导TLR2、3、4和9的表达，而在男性脂肪组织中没有，而且不影响TLR接头MyD88。雌性小鼠血清内毒素升高可能导致脂肪组织炎症。体外慢性酒精介导的巨噬细胞对内毒素的致敏与性别无关。总之，我们首次证明酒精诱导的脂肪组织炎症存在性别二态性，雌性小鼠比雄性小鼠表现出更高程度的炎症。
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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影响因子：
4.6
作者：
Kasztelan-Szczerbinska B;Surdacka A;Slomka M;Rolinski J;Celinski K;Smolen A;Szczerbinski M
通讯作者：
Szczerbinski M
影响因子：
29
作者：
Baker RG;Hayden MS;Ghosh S
通讯作者：
Ghosh S
DOI：
10.1152/ajpgi.1997.272.5.g1186
发表时间：
1997-05-01
影响因子：
4.5
作者：
Iimuro, Y;Frankenberg, MV;Thurman, RG
通讯作者：
Thurman, RG
影响因子：
7.7
作者：
Lumeng, Carey N.;DeYoung, Stephanie M.;Saltiel, Alan R.
通讯作者：
Saltiel, Alan R.
影响因子：
13.5
作者：
Chen, Xiaocong;Sebastian, Becky M.;Tang, Hui;McMullen, Megan M.;Axhemi, Armend;Jacobsen, Donald W.;Nagy, Laura E.
通讯作者：
Nagy, Laura E.