Tanaka Hiroaki, Fukahori Suguru, Baba Shinji, Ueno Takato, Sivakumar Ramadoss, Yagi Minoru, Asagiri Kimio, Ishii Shinji, Tanaka Yoshiaki
Department of Pediatric Surgery, Kurume University School of Medicine, Kurume, Japan.
Department of Pediatric Surgery, Kurume University School of Medicine, Kurume, Japan
JPEN J Parenter Enteral Nutr. 2016 May;40(4):519-28. doi: 10.1177/0148607114555160. Epub 2014 Oct 14.
The aim of the present study was to elucidate whether the administration of antioxidant-rich nutrients, including branched-chain amino acids (BCAAs), microelements, and vitamins, both alone and in combination, has a positive impact on liver function in a nonalcoholic steatohepatitis (NASH) mouse model and identify the mechanisms underlying these effects.
Seven-week-old male KKAy mice fed a methionine- and choline-deficient diet (MCD) for 4 weeks were divided into 7 groups and fed the following planned diets for another 4 weeks: group A (normal diet), group B (MCD; control), group C (MCD with rich microelements), group D (MCD with rich BCAAs), group E (MCD with rich microelements and BCAAs), and group F (MCD with rich microelements, BCAAs, and vitamins). We then conducted biochemical assays, histological analyses, immunohistochemistry for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxy-2'-nonenal (4-HNE), and Western blotting for insulin glucose signaling, lipid metabolism, and endoplasmic reticulum (ER) stress-related signaling in liver specimens obtained from mice in each group.
The morphometric grades of all NASH-related findings and the mean degree of 8-OHdG immunolocalization in groups D-F were significantly lower than those observed in group B. The expression levels of insulin receptor β subunit (IRβ) and p-elF in groups E and F and those of phosphatidyl-inositol 3 kinase (PI3K85), p-AcelCoA, and PERK in group F were similar to those noted in group A.
The administration of a combination of antioxidant-rich nutrients, including BCAAs and microelements, is likely to suppress the progression of NASH by reducing oxidative stress, primarily via the downregulation of the ER stress pathway.
本研究的目的是阐明富含抗氧化剂的营养素，包括支链氨基酸（BCAAs）、微量元素和维生素，单独或联合使用是否对非酒精性脂肪性肝炎（NASH）小鼠模型的肝功能有积极影响，并确定这些作用的潜在机制。
将7周龄雄性KKAy小鼠喂饲蛋氨酸和胆碱缺乏饮食（MCD）4周，然后分为7组，再喂饲以下计划饮食4周：A组（正常饮食）、B组（MCD；对照组）、C组（富含微量元素的MCD）、D组（富含BCAAs的MCD）、E组（富含微量元素和BCAAs的MCD）、F组（富含微量元素、BCAAs和维生素的MCD）。然后，我们对每组小鼠肝脏标本进行生化分析、组织学分析、8-羟基-2'-脱氧鸟苷（8-OHdG）和4-羟基-2'-壬烯醛（4-HNE）的免疫组织化学检测，以及胰岛素葡萄糖信号、脂质代谢和内质网（ER）应激相关信号的蛋白质印迹分析。
D-F组所有NASH相关结果的形态学分级和8-OHdG免疫定位的平均程度均显著低于B组。E组和F组胰岛素受体β亚基（IRβ）和p-elF的表达水平以及F组磷脂酰肌醇3激酶（PI3K85）、p-AcelCoA和PERK的表达水平与A组相似。
给予包括BCAAs和微量元素在内的富含抗氧化剂的营养素组合可能通过降低氧化应激，主要是通过下调ER应激途径来抑制NASH的进展。
