Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome
Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome
复制标题
DOI：
10.1194/jlr.m011205
复制
发表时间：
2011-02-01
影响因子：
6.5
通讯作者：
Kershaw, Erin E.
中科院分区：
文献类型：
--
作者：
Basantani, Mahesh K.;Sitnick, Mitch T.;Kershaw, Erin E.
PNPLA 3（adiponutrin，钙非依赖性磷脂酶A（2）β [iPLA（2）β]）是一种富含脂肪的营养调节蛋白，属于含马铃薯糖样磷脂酶结构域（PNPLA）家族的脂质代谢蛋白。人PNPLA 3基因中的遗传变异（即，rs738409 I148 M等位基因）与脂肪肝疾病有强烈且反复的关联。虽然人PNPLA 3在体外具有三酰甘油（TAG）水解酶和转酰酶活性，但其体内功能和生理相关性仍存在争议。本研究的目的是确定小鼠中Pnpla 3基因的全局靶向缺失的代谢后果。我们发现，Pnpla 3 mRNA的表达在脂肪组织和肝脏中的急性和慢性营养挑战的反应改变。然而，小鼠中Pnpla 3基因的全局靶向缺失不影响TAG水解，也不影响能量/葡萄糖/脂质稳态或肝脂肪变性/损伤。旨在增加Pnpla 3表达的实验干预（再喂养、高蔗糖饮食、饮食诱导的肥胖和肝X受体激动）同样未能揭示上述代谢表型的差异。Pnpla 3蛋白质Pnpla 5的表达在脂肪组织中增加，但在Pnpla 3缺陷小鼠的肝脏中没有增加，但没有鉴定出参与TAG代谢的基因的补偿调节。总之，这些数据反对Pnpla 3功能丧失在小鼠脂肪肝疾病或代谢综合征中的作用。Basantani，M. K.，M. T.西特尼克湖Cai，C. S. Brenner，N. P. Gardner，J. Z. Li，G.舍斯沃尔湾杨，M.库马里河，巴西-地W.格罗斯河Zechner和E. E.克肖Pnpla 3/Adiponutrin缺乏小鼠不会导致脂肪肝或代谢综合征。J. Lipid Res. 2011. 52：318-329。
PNPLA3 (adiponutrin, calcium-independent phospholipase A(2) epsilon [iPLA(2)epsilon]) is an adipose-enriched, nutritionally regulated protein that belongs to the patatin-like phospholipase domain containing (PNPLA) family of lipid metabolizing proteins. Genetic variations in the human PNPLA3 gene (i.e., the rs738409 I148M allele) has been strongly and repeatedly associated with fatty liver disease. Although human PNPLA3 has triacylglycerol (TAG) hydrolase and transacylase activities in vitro, its in vivo function and physiological relevance remain controversial. The objective of this study was to determine the metabolic consequences of global targeted deletion of the Pnpla3 gene in mice. We found that Pnpla3 mRNA expression is altered in adipose tissue and liver in response to acute and chronic nutritional challenges. However, global targeted deletion of the Pnpla3 gene in mice did not affect TAG hydrolysis, nor did it influence energy/glucose/lipid homoeostasis or hepatic steatosis/injury. Experimental interventions designed to increase Pnpla3 expression (refeeding, high-sucrose diet, diet-induced obesity, and liver X receptor agonism) likewise failed to reveal differences in the above-mentioned metabolic phenotypes. Expression of the Pnpla3 paralog, Pnpla5, was increased in adipose tissue but not in liver of Pnpla3 deficient mice, but compensatory regulation of genes involved in TAG metabolism was not identified. Together these data argue against a role for Pnpla3 loss-of-function in fatty liver disease or metabolic syndrome in mice.-Basantani, M. K., M. T. Sitnick, L. Cai, D. S. Brenner, N. P. Gardner, J. Z. Li, G. Schoiswohl, K. Yang, M. Kumari, R. W. Gross, R. Zechner, and E. E. Kershaw. Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome. J. Lipid Res. 2011. 52: 318-329.