Hepatic Transcriptome Profiles of Mice with Diet-Induced Nonalcoholic Steatohepatitis Treated with Astaxanthin and Vitamin E.
Hepatic Transcriptome Profiles of Mice with Diet-Induced Nonalcoholic Steatohepatitis Treated with Astaxanthin and Vitamin E.
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DOI：
10.3390/ijms18030593
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发表时间：
2017-03-08
影响因子：
5.6
通讯作者：
Ota T
中科院分区：
文献类型：
--
作者：
Kobori M;Takahashi Y;Sakurai M;Ni Y;Chen G;Nagashimada M;Kaneko S;Ota T
虾青素可减轻高胆固醇、高胆固醇和高脂肪（CL）饮食诱导的非酒精性脂肪性肝炎（NASH）小鼠的肝脏脂质积累和过氧化、炎症和纤维化。它被认为是一种抑制人类NASH进展的潜在新疗法。在这项研究中，我们比较了虾青素或抗氧化剂维生素E治疗CL饮食诱导的NASH小鼠的肝脏基因表达谱。使用DNA微阵列对喂食含有虾青素或维生素E的标准、CL或CL饮食12周的小鼠肝脏进行全面的基因表达分析。虾青素和维生素E都能有效改善与真核起始因子-2 （EIF2）信号相关的基因表达，该信号在NASH中被肝脏内质网（ER）应激抑制。然而，虾青素并没有改善线粒体功能障碍相关基因的表达。虾青素，而不是维生素E，可以抑制配体依赖性核受体过氧化物酶体增殖体激活受体(PPAR) α (PPARA)和PPARδ (PPARD)的作用，并影响相关分子。利用虾青素建立一种新的治疗方法需要阐明虾青素对饮食诱导NASH小鼠肝脏中PPARα和相关分子功能的分子作用。
Astaxanthin alleviates hepatic lipid accumulation and peroxidation, inflammation, and fibrosis in mice with high-cholesterol, high-cholate, and high-fat (CL) diet-induced nonalcoholic steatohepatitis (NASH). It has been proposed as a potential new treatment to inhibit the progression of NASH in humans. In this study, we compared hepatic gene expression profiles after treatment with astaxanthin or the antioxidant vitamin E in mice with CL diet-induced NASH. Comprehensive gene expression analyses of the livers of mice fed a standard, CL, or CL diet containing astaxanthin or vitamin E for 12 weeks were performed using a DNA microarray. Both astaxanthin and vitamin E effectively improved gene expression associated with eukaryotic initiation factor-2 (EIF2) signaling, which is suppressed in NASH by endoplasmic reticulum (ER) stress in the liver. However, astaxanthin did not improve the expression of genes associated with mitochondrial dysfunction. Astaxanthin, but not vitamin E, was predicted to suppress the actions of ligand-dependent nuclear receptors peroxisome proliferator-activated receptors, (PPAR) α (PPARA) and PPARδ (PPARD), and to affect related molecules. Establishing a new therapy using astaxanthin will require elucidation of astaxanthin’s molecular action on the functions of PPARα and related molecules in the livers of mice with diet-induced NASH.