Small heterodimer partner deletion prevents hepatic steatosis and when combined with farnesoid X receptor loss protects against type 2 diabetes in mice.
Small heterodimer partner deletion prevents hepatic steatosis and when combined with farnesoid X receptor loss protects against type 2 diabetes in mice.
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DOI：
10.1002/hep.29305
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Anakk S
中科院分区：
文献类型：
--
作者：
Akinrotimi O;Riessen R;VanDuyne P;Park JE;Lee YK;Wong LJ;Zavacki AM;Schoonjans K;Anakk S
核受体法尼醇X受体（FXR）和小异二聚体伴侣（SHP）是胆汁酸、脂质和葡萄糖内稳态的重要调节因子。在此我们表明，在高脂饮食刺激下，全身性Fxr -/- Shp -/-双敲除（DKO）小鼠不易出现体重增加、葡萄糖耐受不良和肝脏脂肪变性。DKO小鼠天生具有增强的脂肪燃烧能力，并能抑制肝脏从头脂质合成。此外，DKO小鼠也非常活跃，这与在骨骼肌中观察到的磷酸烯醇式丙酮酸羧激酶（Pepck）表达增加、ⅠA型纤维和线粒体功能增强密切相关。从机制上讲，我们证明肝脏特异性Shp缺失通过抑制过氧化物酶体增殖物激活受体γ2（Pparγ2）和脂滴蛋白Fsp27β的表达来防止脂肪肝的发生。结论：这些数据表明FXR和SHP失活可能有利于对抗饮食诱导的肥胖，并揭示肝脏SHP对于促进脂肪肝疾病是必需的。
Nuclear receptors Farnesoid X Receptor (FXR) and Small Heterodimer Partner (SHP) are important regulators of bile acid, lipid and glucose homeostasis. Here we show that global Fxr −/− Shp−/− double knockout (DKO) mice are refractory to weight gain, glucose intolerance and hepatic steatosis when challenged with high-fat diet. DKO mice display an inherently increased capacity to burn fat and suppress de novo hepatic lipid synthesis. Moreover, DKO mice are also very active and that correlates well with the observed increase in Pepck expression, type IA fibers and mitochondrial function in the skeletal muscle. Mechanistically, we demonstrate that liver-specific Shp deletion protects against fatty liver development by suppressing the expression of Pparγ2 and lipid-droplet protein Fsp27β. Conclusions: These data suggest that Fxr and Shp inactivation may be beneficial to combat diet-induced obesity and uncover that hepatic SHP is necessary to promote fatty liver disease.
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影响因子：
25.7
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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Glecaprevir和Pibrentasvir进行12周的丙型肝炎病毒基因型感染和事先直接作用抗病毒药治疗。
DOI：
10.1002/hep.29081
发表时间：
2017-08
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Poordad F;Felizarta F;Asatryan A;Sulkowski MS;Reindollar RW;Landis CS;Gordon SC;Flamm SL;Fried MW;Bernstein DE;Lin CW;Liu R;Lovell SS;Ng TI;Kort J;Mensa FJ
通讯作者：
Mensa FJ