IMM-H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high-fat diet.
IMM-H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high-fat diet.
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DOI：
10.1002/2211-5463.12272
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发表时间：
2017-09
期刊：
影响因子：
2.6
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
Shi H;Wang Q;Yang L;Xie S;Zhu H
非酒精性脂肪性肝病（NAFLD）是人类最常见的慢性肝病，其特征在于肝细胞中三酰甘油（TG）的积累。我们测试了2′，3 ′，5 ′-三乙酰基-N6-（3-羟基苯胺）腺苷（IMM-H 007）是否可以消除喂食高脂饮食（HFD）的仓鼠（作为NAFLD模型）的肝脂肪变性。与仅HFD对照相比，IMM-H 007治疗显著降低了喂食HFD的仓鼠的血清TG、总胆固醇和游离脂肪酸（FFA）水平，血清转氨酶和空腹胰岛素水平显著降低，而不影响空腹血糖水平。此外，1H-MRI和组织病理学分析显示，IMM-H 007治疗改善了肝脏脂质蓄积和纤维化。这些变化伴随着胰岛素抵抗和氧化应激的改善以及炎症的减轻。IMM-H 007降低参与肝脏脂肪酸摄取和脂肪生成的蛋白质的表达，并增加极低密度脂蛋白分泌和负责脂肪酸氧化和自噬的蛋白质的表达。在体内研究中，IMM-H 007抑制脂肪酸输入肝细胞和肝脏脂肪生成，同时刺激脂肪酸氧化，自噬和肝脏脂质输出。这些数据表明，IMM-H 007通过调节脂质代谢解决HFD喂养仓鼠的肝脂肪变性。因此，IMM-H 007具有治疗NAFLD的潜力。
Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in humans, is characterized by the accumulation of triacylglycerols (TGs) in hepatocytes. We tested whether 2′,3′,5′‐tri‐acetyl‐N6‐(3‐hydroxylaniline) adenosine (IMM‐H007) can eliminate hepatic steatosis in hamsters fed a high‐fat diet (HFD), as a model of NAFLD. Compared with HFD‐only controls, IMM‐H007 treatment significantly lowered serum levels of TG, total cholesterol, and free fatty acids (FFAs) in hamsters fed the HFD, with a prominent decrease in levels of serum transaminases and fasting insulin, without affecting fasting glucose levels. Moreover, 1H‐MRI and histopathological analyses revealed that hepatic lipid accumulation and fibrosis were improved by IMM‐H007 treatment. These changes were accompanied by improvement of insulin resistance and oxidative stress, and attenuation of inflammation. IMM‐H007 reduced expression of proteins involved in uptake of hepatic fatty acids and lipogenesis, and increased very low density lipoprotein secretion and expression of proteins responsible for fatty acid oxidation and autophagy. In studies in vivo, IMM‐H007 inhibited fatty acid import into hepatocytes and liver lipogenesis, and concomitantly stimulated fatty acid oxidation, autophagy, and export of hepatic lipids. These data suggest that IMM‐H007 resolves hepatic steatosis in HFD‐fed hamsters by the regulation of lipid metabolism. Thus, IMM‐H007 has therapeutic potential for NAFLD.
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影响因子：
13.5
作者：
Fujita, Koji;Nozaki, Yuichi;Nakajima, Atsushi
通讯作者：
Nakajima, Atsushi
影响因子：
6.5
作者：
Millar, JS;Cromley, DA;Billheimer, JT
通讯作者：
Billheimer, JT
影响因子：
6
作者：
Araya, J;Rodrigo, R;Poniachik, J
通讯作者：
Poniachik, J
DOI：
10.1073/pnas.0404297101
发表时间：
2004-08-03
影响因子：
11.1
作者：
Chen, GX;Liang, GS;Brown, MS
通讯作者：
Brown, MS
影响因子：
64.8
作者：
Minokoshi, Y;Kim, YB;Kahn, BB
通讯作者：
Kahn, BB