Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease.
Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease.
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DOI：
10.1002/hep.23812
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发表时间：
2010-09
期刊：
影响因子：
13.5
通讯作者：
Chan, Lawrence
中科院分区：
文献类型：
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作者：
Chen, Weiqin;Chang, Benny;Li, Lan;Chan, Lawrence
PNPLA 3（Adiponutrin）是一种新型的含有patatin样磷脂酶结构域的酶，在脂肪中高水平表达，但也在包括肝脏在内的其他组织中表达。PNPLA 3的多态性与肥胖和胰岛素敏感性有关。值得注意的是，PNPLA 3基因的非同义变体rs738409（G）等位基因被发现与非酒精性和酒精性脂肪肝疾病密切相关。我们通过基因靶向产生了Pnpla 3 −/−小鼠。Pnpla 3的缺失对体重或组成、脂肪量或发育没有影响，无论小鼠是被喂食常规食物还是高脂肪饮食还是被饲养成Lepob/ob背景。当Pnpla 3 +/+和Pnpla 3 −/−小鼠正常进食、喂食三种不同的脂肪肝诱导饮食或饲养到Lepob/ob背景后，血浆和肝脏甘油三酯含量以及血浆天冬氨酸转氨酶和丙氨酸转氨酶水平没有差异。肝脏Pnpla 5 mRNA水平在野生型和Pnpla 3 −/−小鼠中相似，但脂肪Pnpla 5 mRNA水平在Pnpla 3 −/−小鼠中增加。高蔗糖脂肪生成饮食刺激肝脏Pnpla 3和Pnpla 5 mRNA水平达到相似的程度，但它不影响Pnpla 3 +/+和Pnpla 3 −/−小鼠的脂肪或肝脏甘油三酯脂肪酶（ATGL，又名Pnpla 2）mRNA。最后，Pnpla 3 +/+和Pnpla 3 −/−小鼠在常规食物或三种不同的脂肪肝诱导饮食中显示出相似的葡萄糖耐量和胰岛素耐量测试。结论：Pnpla 3的缺失不会导致小鼠脂肪肝、肝酶升高或胰岛素抵抗。
PNPLA3 (Adiponutrin), a novel patatin-like phospholipase domain-containing enzyme, is expressed at high level in fat, but also in other tissues including liver. Polymorphisms in PNPLA3 have been linked to obesity and insulin sensitivity. Notably, a nonsynonymous variant rs738409(G) allele of the PNPLA3 gene was found to be strongly associated with both non-alcoholic and alcoholic fatty liver disease. We have generated Pnpla3−/− mice by gene targeting. Loss of Pnpla3 has no effect on body weight or composition, adipose mass or development, whether the mice were fed regular chow or high-fat diet or bred into Lepob/ob background. Plasma and liver triglyceride content and plasma aspartate aminotransferase and alanine aminotransferase levels were not different between Pnpla3+/+ and Pnpla3−/− mice while they were on regular chow, fed three different fatty liver-inducing diets, or after they were bred into Lepob/ob background. Hepatic Pnpla5 mRNA levels were similar in wild-type and Pnpla3−/− mice, though adipose Pnpla5 mRNA level was increased in Pnpla3−/− mice. A high sucrose lipogenic diet stimulated hepatic Pnpla3 and Pnpla5 mRNA levels to a similar degree, but it did not affect adipose or liver triglyceride lipase (ATGL, aka Pnpla2) mRNA in Pnpla3+/+ and Pnpla3−/− mice. Finally, Pnpla3+/+ and Pnpla3−/− mice displayed similar glucose tolerance and insulin tolerance tests while on regular chow or three different fatty liver-inducing diets. Conclusion: Loss of Pnpla3 does not cause fatty liver, liver enzyme elevation, or insulin resistance in mice.
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携带 patatin 样磷脂酶 3 基因变体的人类脂肪肝与胰岛素抵抗之间的关联。
影响因子：
7.7
作者：
Kantartzis K;Peter A;Machicao F;Machann J;Wagner S;Königsrainer I;Königsrainer A;Schick F;Fritsche A;Häring HU;Stefan N
通讯作者：
Stefan N
影响因子：
7.7
作者：
Johansson, LE;Hoffstedt, J;Ridderstråle, M
通讯作者：
Ridderstråle, M
影响因子：
6.5
作者：
Lake, AC;Sun, Y;Gimeno, RE
通讯作者：
Gimeno, RE
影响因子：
56.9
作者：
Haemmerle, G;Lass, A;Zechner, R
通讯作者：
Zechner, R
DOI：
10.1074/jbc.m109.064501
发表时间：
2010-02-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
He S;McPhaul C;Li JZ;Garuti R;Kinch L;Grishin NV;Cohen JC;Hobbs HH
通讯作者：
Hobbs HH