Deficient copper concentrations in dried-defatted hepatic tissue from ob/ob mice: A potential model for study of defective copper regulation in metabolic liver disease.

Deficient copper concentrations in dried-defatted hepatic tissue from ob/ob mice: A potential model for study of defective copper regulation in metabolic liver disease.
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ob/ob小鼠干燥的肝组织中的铜浓度不足:研究代谢肝病中有缺陷的铜调节的潜在模型。

DOI:
10.1016/j.bbrc.2015.03.067
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发表时间:
2015-05-08
影响因子:
3.1
通讯作者:
Cooper, Garth J. S.
Cooper, Garth J. S.
中科院分区:
生物学4区
文献类型:
--
作者:
Church, Stephanie J.;Begley, Paul;Kureishy, Nina;McHarg, Selina;Bishop, Paul N.;Bechtold, David A.;Unwin, Richard D.;Cooper, Garth J. S.

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Ob/ob小鼠为肥胖和2型糖尿病患者的非酒精性脂肪性肝病/非酒精性脂肪性肝炎(NAFLD/NASH)提供了动物模型。低肝脏铜与低铜饮食引起的全身性铜缺乏症动物的肝脏脂质积聚(脂肪变性)有关。然而,NAFLD或NASH患者的肝铜状态尚不确定,并且缺乏可用于研究常见形式的代谢性肝病中肝铜调节的经验证的动物模型。在这里,我们报告平行测量的基本金属水平在全肝组织和脱脂干肝组织从肥胖/肥胖和非肥胖对照小鼠。在发生NAFLD/NASH的年龄,对ob/ob小鼠的全肝组织进行测量,为脂肪变性导致铜和所有其他必需金属的降低提供了令人信服的证据,因此不能用于研究该模型中的肝脏金属调节。与此形成鲜明对比的是,脱脂干肝样品中的金属测量结果显示,大多数必需金属实际上是正常的,并表明ob/ob小鼠中铜的特定降低,与肝铜缺乏一致。因此,ob/ob小鼠可以提供用于研究NAFLD和NASH中的铜调节的模型,只要在脱脂干燥的肝组织中测量水平。Ob/ob小鼠发生肝铜缺乏。铜缺乏与NAFLD/NASH一起发展。整个组织中的金属测量受到浸润脂肪的影响。当在整个肝脏中测量时,所有必需金属的水平在ob/ob小鼠中较低。在脂肪提取后,金属水平是正常的,除了铜。
Ob/ob mice provide an animal model for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) in patients with obesity and type-2 diabetes. Low liver copper has been linked to hepatic lipid build-up (steatosis) in animals with systemic copper deficiency caused by low-copper diets. However, hepatic copper status in patients with NAFLD or NASH is uncertain, and a validated animal model useful for the study of hepatic copper regulation in common forms of metabolic liver disease is lacking. Here, we report parallel measurements of essential metal levels in whole-liver tissue and defatted-dried liver tissue from ob/ob and non-obese control mice. Measurements in whole-liver tissue from ob/ob mice at an age when they have developed NAFLD/NASH, provide compelling evidence for factitious lowering of copper and all other essential metals by steatosis, and so cannot be used to study hepatic metal regulation in this model. By marked contrast, metal measurements in defatted-dried liver samples reveal that most essential metals were actually normal and indicate specific lowering of copper in ob/ob mice, consistent with hepatic copper deficiency. Thus ob/ob mice can provide a model useful for the study of copper regulation in NAFLD and NASH, provided levels are measured in defatted-dried liver tissue. Ob/ob mice develop hepatic copper deficiency. Copper deficiency develops alongside NAFLD/NASH. Metal measurements in whole tissue are impacted by infiltrating fat. Levels of all essential metals are lower in ob/ob mice when measured in whole liver. After fat extraction, metal levels are normal, with the exception of copper.
DOI: 10.3181/00379727-204-43640
发表时间: 1993-10-01
影响因子: --
作者:
ALOTHMAN, AA;ROSENSTEIN, F;LEI, KY
通讯作者: LEI, KY
DOI: 10.1093/jn/127.5.838s
发表时间: 1997-05-01
期刊: The Journal of nutrition
影响因子: --
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发表时间: 2014-06-14
影响因子: 9.3
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发表时间: 2003-07-01
影响因子: 15.9
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通讯作者: Cooper, GJS