Kakazu Eiji, Sano Akitoshi, Morosawa Tatsuki, Inoue Jun, Ninomiya Masashi, Iwata Tomoaki, Nakamura Takuya, Takai Satoshi, Sawada Shojiro, Katagiri Hideki, Shimosegawa Tooru, Masamune Atsushi
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Division of Gastroenterology, Saka General Hospital, Shiogama, Japan.
Hepatol Res. 2019 Aug;49(8):860-871. doi: 10.1111/hepr.13346. Epub 2019 May 21.
Macrovesicular steatosis around the central vein (zone 3) is one of the pathological features of non-alcoholic fatty liver disease or steatohepatitis (NAFLD/NASH). The aim of this study is to elucidate precisely the association between the area of lipid droplets (LDs) and the plasma metabolic parameters in patients with NAFLD/NASH.
Eighty patients with NAFLD/NASH diagnosed by needle biopsy were enrolled. The LDs around zone 3 were counted automatically by image processing software, the total area of LDs (TLDs), the maximum area of LDs (MAXLDs), the average area of LDs (AVELDs) and the heterogeneity by the coefficient of variation (CV [%]) were quantified. The correlations between these values and plasma metabolic parameters were analyzed. We evaluated the association between branched chain amino acids (BCAAs) and the heterogeneity of LDs in hepatocytes in vitro and in vivo.
The MAXLDs was significantly correlated with more metabolic parameters than AVELDs and TLDs. The level of BCAAs was independently associated with the CV among the metabolic parameters. In early stage NAFLD, aspartate and alanine aminotransferase were significantly higher in the high CV group than in the low CV group. The high concentration of BCAAs increased the CV of LDs in hepatocytes accompanied by the expression of phosphor-p70 S6 kinase and sterol regulatory element-binding protein 1 in vitro. A high BCAA diet induced high heterogeneity of LDs around zone 3 in ob/ob mice.
The levels of BCAAs were associated with the LD heterogeneity of hepatocytes around zone 3 in patients with NAFLD/NASH.
中央静脉周围（3区）的大泡性脂肪变性是非酒精性脂肪性肝病或脂肪性肝炎（NAFLD/NASH）的病理特征之一。本研究的目的是精确阐明NAFLD/NASH患者中脂滴（LDs）面积与血浆代谢参数之间的关联。
纳入80例经穿刺活检确诊为NAFLD/NASH的患者。通过图像处理软件自动计数3区周围的LDs，对LDs的总面积（TLDs）、最大面积（MAXLDs）、平均面积（AVELDs）以及变异系数（CV [%]）表示的异质性进行量化。分析这些值与血浆代谢参数之间的相关性。我们在体外和体内评估了支链氨基酸（BCAAs）与肝细胞中LDs异质性之间的关联。
与AVELDs和TLDs相比，MAXLDs与更多的代谢参数显著相关。在代谢参数中，BCAAs水平与CV独立相关。在早期NAFLD中，高CV组的天冬氨酸和丙氨酸转氨酶显著高于低CV组。在体外，高浓度的BCAAs增加了肝细胞中LDs的CV，并伴有磷酸化p70 S6激酶和固醇调节元件结合蛋白1的表达。高BCAA饮食诱导ob/ob小鼠3区周围LDs的高度异质性。
NAFLD/NASH患者的BCAAs水平与3区周围肝细胞的LD异质性相关。
