Ishiyama Shiori, Kimura Mayu, Umihira Nodoka, Matsumoto Sachi, Takahashi Atsushi, Nakagawa Takao, Wakayama Teruhiko, Kishigami Satoshi, Mochizuki Kazuki
Department of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi, 400-8510, Japan.
Graduate School of Life and Environmental Sciences, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi, 400-8510, Japan.
Biochem Biophys Rep. 2021 May 30;27:101029. doi: 10.1016/j.bbrep.2021.101029. eCollection 2021 Sep.
Non-alcoholic fatty liver disease (NAFLD), which includes the subtype non-alcoholic steatohepatitis (NASH), is a major complication of type 2 diabetic mellitus (T2DM), even among non-obese patients. However, the exact cause of NAFLD/NASH in non-obese patients with T2DM is unclear. We studied a non-obese mouse model of T2DM created through the malnourishment of embryos by culture for 48 h in α-minimum essential medium (MEM) at the two-cell stage. We compared the development of steatohepatitis in these MEM mice with control mice that were similarly cultured in standard potassium simplex-optimized medium (KSOM). We also studied the effects of 10 weeks of consumption of barley, which contains large amounts of the soluble fiber β-glucan, on the steatohepatitis of the adult MEM mice. The size of lipid droplets, the area of fibrosis, and the mRNA expression of the transforming growth factor beta () gene in the liver were higher in adult MEM mice fed a rice-based diet than in KSOM mice fed the same diet. However, barley consumption reduced the area of fibrosis and TGFB expression in MEM mice. In conclusion, adult mice that are cultured in MEM at the two-cell embryo stage develop steatohepatitis and T2DM, accompanied by higher hepatic TGFB expression, than KSOM controls. Furthermore, the consumption of barley during adulthood ameliorates the steatohepatitis and reduces the TGFB expression.
非酒精性脂肪性肝病(NAFLD),包括非酒精性脂肪性肝炎(NASH)亚型,是2型糖尿病(T2DM)的主要并发症,即使在非肥胖患者中也是如此。然而,非肥胖T2DM患者发生NAFLD/NASH的确切原因尚不清楚。我们研究了一种通过在双细胞阶段于α-最低必需培养基(MEM)中培养胚胎48小时使其营养不良而建立的非肥胖T2DM小鼠模型。我们将这些MEM小鼠与在标准钾离子单倍体优化培养基(KSOM)中进行类似培养的对照小鼠的脂肪性肝炎发展情况进行了比较。我们还研究了连续10周食用含有大量可溶性纤维β-葡聚糖的大麦对成年MEM小鼠脂肪性肝炎的影响。与喂食相同饮食的KSOM小鼠相比,喂食大米为主饮食的成年MEM小鼠肝脏中脂滴大小、纤维化面积以及转化生长因子β(TGFβ)基因的mRNA表达更高。然而,食用大麦可减少MEM小鼠的纤维化面积和TGFβ表达。总之,在双细胞胚胎阶段于MEM中培养的成年小鼠比KSOM对照小鼠更容易发生脂肪性肝炎和T2DM,且伴有更高的肝脏TGFβ表达。此外,成年期食用大麦可改善脂肪性肝炎并降低TGFβ表达。