Uchiyama Hironobu, Komatsu Ken-Ichi, Nakata Akifumi, Sato Keisuke, Mihara Yoshihiro, Takaguri Akira, Nagashima Takayuki, Wakame Koji
Genome Research Center, Tokyo University of Agriculture, Tokyo, Japan.
Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Hokkaido, Japan.
Anticancer Res. 2018 Jul;38(7):4305-4311. doi: 10.21873/anticanres.12729.
BACKGROUND/AIM: Mulberry (Morus alba L.) leaves (ML) contain many functional components, such as 1-deoxynojirimycin, flavonoids (rutin, quercetin, kaempferol). It is well known that 1-deoxynojirimycin functions to suppress increases in blood glucose level by α-glucosidase inhibitory activity. Thus, the molecular mechanism underlying the protective and therapeutic effects of ML supplementation was investigated on a mouse model of high-calorie diet (Western diet: WD)-induced hepatic steatosis (HS).
The C57BL/6J mouse was used for the HS model. The mice were divided into three groups: control (normal diet: ND), WD, and WD + 1% ML groups. The WD group was fed a high-calorie (high carbohydrate and high fat) diet for 12 weeks to develop HS. At week 12, all mice were sacrificed, blood was collected for biochemical tests, and the liver was obtained for histological examination and RNA sequencing (RNA-Seq).
Liver weight, plasma triglycerides (TG), alanine aminotransferase (ALT), and alanine aminotransferase (AST) levels of both ML groups were significantly lower than those of the WD group. On histological examination of the liver, the area of fatty deposits was found to be suppressed by ML administration. In the gene expression analysis of the liver of WD- versus ML-fed mice by RNA-Seq, 722/45,706 genes exhibited a significant change in expression (corrected p-value<0.05). Gene network analysis of these genes showed that genes related to liver inflammation were inactivated and those related to regeneration of liver were activated in the ML group.
ML functions to suppress HS in WD-fed mice and regulates genes related to inflammation and regeneration of liver cells.
背景/目的：桑叶（桑科植物桑的叶子）含有多种功能成分，如1-脱氧野尻霉素、黄酮类化合物（芦丁、槲皮素、山奈酚）。众所周知，1-脱氧野尻霉素通过α-葡萄糖苷酶抑制活性发挥抑制血糖水平升高的作用。因此，本研究在高热量饮食（西式饮食：WD）诱导的肝脂肪变性（HS）小鼠模型上，探讨了补充桑叶的保护和治疗作用的分子机制。
使用C57BL/6J小鼠建立HS模型。将小鼠分为三组：对照组（正常饮食：ND）、WD组和WD + 1%桑叶组。WD组喂食高热量（高碳水化合物和高脂肪）饮食12周以诱导HS。在第12周时，处死所有小鼠，采集血液进行生化检测，并获取肝脏进行组织学检查和RNA测序（RNA-Seq）。
两个桑叶组的肝脏重量、血浆甘油三酯（TG）、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平均显著低于WD组。肝脏组织学检查发现，给予桑叶可抑制脂肪沉积面积。通过RNA-Seq对WD喂养小鼠与桑叶喂养小鼠的肝脏进行基因表达分析，722/45706个基因表现出显著的表达变化（校正p值<0.05）。对这些基因的基因网络分析表明，在桑叶组中，与肝脏炎症相关的基因失活，与肝细胞再生相关的基因被激活。
桑叶具有抑制WD喂养小鼠HS的作用，并调节与肝细胞炎症和再生相关的基因。
