α-Tocopherol suppresses hepatic steatosis by increasing CPT-1 expression in a mouse model of diet-induced nonalcoholic fatty liver disease.
α-Tocopherol suppresses hepatic steatosis by increasing CPT-1 expression in a mouse model of diet-induced nonalcoholic fatty liver disease.
复制标题
α-生育酚通过增加饮食诱导的非酒精性脂肪性肝病小鼠模型中CPT-1的表达来抑制肝脏脂肪变性。
DOI：
10.1002/osp4.460
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发表时间：
2021-03
影响因子：
2.2
通讯作者：
Shibata H
中科院分区：
文献类型：
--
作者：
Tokoro M;Gotoh K;Kudo Y;Hirashita Y;Iwao M;Arakawa M;Endo M;Oribe J;Masaki T;Honda K;Kakuma T;Seike M;Murakami K;Shibata H
抗氧化治疗与维生素E似乎是有效的治疗非酒精性脂肪性肝病（NAFLD）。然而，其作用机制和最佳治疗剂量尚不清楚。本研究旨在研究α‐生育酚（α‐Toc）在饮食诱导的肥胖模型中对NAFLD的影响是否具有剂量依赖性。雄性小鼠分别饲喂标准饲料、高脂（HF）饲粮、高脂饲粮中添加低剂量或高剂量α - Toc。评估组织学结果、甘油三酯含量和与脂肪酸合成/氧化相关的蛋白质表达水平，如肝脏肉碱棕榈酰转移酶I （CPT‐1）。此外，将CPT - 1抑制剂2 -十四烷基甘糖酸（TDGA）给予喂食低剂量α - Toc的HF饲料小鼠。最后，用0-50 μM α - Toc处理脂肪负载环境下的HepG2细胞。低剂量α - Toc治疗可减少HF诱导的肝脏脂肪堆积，但在高剂量α - Toc治疗中未观察到这一发现。低剂量α - Toc可减弱HF诱导的CPT - 1的还原，而高剂量α - Toc则不能。TDGA抑制低剂量α - Toc诱导的肝脏组织学改善。低剂量α‐Toc作用下，HepG2细胞中CPT‐1的表达增加，而高剂量α‐Toc作用下，CPT‐1的表达不增加。观察到α‐Toc对CPT‐1蛋白水平的双重作用。维生素E对NAFLD的影响可能不是剂量依赖性的。
Antioxidant therapy for with vitamin E appears to be effective for the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanism of action and optimal therapeutic dosage is unclear. The present study was undertaken to examine whether the effects of α‐tocopherol (α‐Toc) on NAFLD are dose‐dependent in a diet‐induced obese model. Male mice were fed standard chow, high‐fat (HF) diet, HF diet with low‐dose, or with high dose of α‐Toc supplementation. Histological findings, triglyceride content, and the levels of protein expression related to fatty acid synthesis/oxidation such as carnitine palmitoyltransferase I (CPT‐1) of liver were evaluated. In addition, 2‐tetradecylglycidic acid (TDGA), a CPT‐1 inhibitor, was administered to mice fed HF diet with low‐dose of α‐Toc. Finally, HepG2 cells in fat‐loaded environment were treated with 0–50 μM α‐Toc. Treatment of low‐dose of α‐Toc decreased HF‐induced hepatic fat accumulation, but this finding was not observed in treatment of high dose of α‐Toc. HF‐induced reduction of CPT‐1 was attenuated with low‐dose of α‐Toc but not with high dose of α‐Toc. TDGA suppressed the improvement of histological findings in liver induced by low‐dose of α‐Toc treatment. CPT‐1 expression in HepG2 cells increased in response to low‐dose of α‐Toc, but not in high dose. Dual action of α‐Toc on CPT‐1 protein levels was observed. The effect of vitamin E on NAFLD may be not be dose‐dependent.
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影响因子：
4.3
作者：
Asaoka Y;Terai S;Sakaida I;Nishina H
通讯作者：
Nishina H
DOI：
10.1111/j.1600-0773.1993.tb01563.x
发表时间：
1993-10-01
期刊：
PHARMACOLOGY & TOXICOLOGY
影响因子：
--
作者：
ANDERSEN, HR;ANDERSEN, O
通讯作者：
ANDERSEN, O
影响因子：
13.5
作者：
Kleiner, DE;Brunt, EM;Sanyal, AJ
通讯作者：
Sanyal, AJ
DOI：
10.3904/kjim.2015.30.5.571
发表时间：
2015-09
期刊：
The Korean journal of internal medicine
影响因子：
--
作者：
Niki E
通讯作者：
Niki E
影响因子：
2.5
作者：
Kuraji, Ryutaro;Fujita, Miyako;Numabe, Yukihiro
通讯作者：
Numabe, Yukihiro