Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.
Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.
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DOI：
10.18632/oncotarget.10506
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发表时间：
2016-07-26
期刊：
影响因子：
--
通讯作者：
Jung YS
中科院分区：
文献类型：
--
作者：
Lee YH;Kim SH;Kim SN;Kwon HJ;Kim JD;Oh JY;Jung YS
男性对代谢性疾病的易感性较高，说明两性异形在发病机制中的重要性。我们假设男性非酒精性脂肪肝发病率较高与肝脏和脂肪组织之间的性别特异性代谢相互作用有关。在本研究中，我们使用蛋氨酸-胆碱缺乏（MCD）饮食诱导的脂肪肝小鼠模型来研究肝脏和脂肪组织代谢反应的性别差异。在mcd饮食2周后，以性别特异性的方式诱导脂肪肝，对雄性小鼠的影响比雌性小鼠更严重。mcd饮食增加雄性小鼠性腺白色脂肪组织（gWAT）中的脂溶酶，而增加雌性小鼠性腺白色脂肪组织中解偶联蛋白1和其他棕色脂肪细胞标志物的表达。此外，与雄性小鼠的gWAT相比，雌性小鼠的gWAT表现出更高的耗氧量和线粒体含量。MCD饮食增加了FGF21在肝组织中的表达，且雌性小鼠肝脏中FGF21的表达上调程度明显更高。在一定程度上，FGF21的内分泌作用是性腺白色脂肪组织的性别特异性褐化的部分原因。总的来说，这些数据表明，雌性特有的白色脂肪组织褐化有助于保护雌性小鼠免受MCD饮食诱导的脂肪肝疾病的侵害。
Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.
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影响因子：
29
作者：
Kajimura S;Spiegelman BM;Seale P
通讯作者：
Seale P
DOI：
10.1152/ajpendo.00009.2005
发表时间：
2005-10-01
影响因子：
5.1
作者：
Granneman, JG;Li, PP;Lu, YY
通讯作者：
Lu, YY
影响因子：
2.1
作者：
FOSTER, DO;FRYDMAN, ML
通讯作者：
FRYDMAN, ML
DOI：
10.1046/j.1440-1746.2003.03198.x
发表时间：
2003-11-01
影响因子：
4.1
作者：
Kirsch, R;Clarkson, V;Hall, PD
通讯作者：
Hall, PD
人类脂肪肝病：旧问题和新见解。
DOI：
10.1126/science.1204265
发表时间：
2011-06-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cohen JC;Horton JD;Hobbs HH
通讯作者：
Hobbs HH