Department of Medicine, Graduate School, Yonsei University College of Medicine, Seoul, South Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, South Korea.
Sci Rep. 2022 Aug 10;12(1):13595. doi: 10.1038/s41598-022-15550-7.
The α-glucosidase inhibitor (α-GI) delays the intestinal absorption of glucose, which reduces postprandial hepatic glucose intake. This mechanism is considered to be effective in treating non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of voglibose, an α-glucosidase inhibitor, on high-fat, high-fructose (HFHFr) diet-induced NAFLD models. Seven-week-old male C57BL/6J mice were randomly placed in a chow diet group or an HFHFr diet group. After 10 weeks, mice in the HFHFr group were randomly assigned to one of three groups: HFHFr diet with vehicle, HFHFr with voglibose, or HFHFr with pioglitazone. Each diet and treatment was continued for 10 weeks. The HFHFr diet induced severe NAFLD in terms of steatosis, hepatitis, and fibrosis. Administration of voglibose improved all aspects of NAFLD, comparable to those of pioglitazone, a positive control. In voglibose-treated mice, gene expressions of hepatic lipogenesis markers were significantly downregulated. In the in vitro experiment, reducing the influx of glucose into hepatocytes significantly reduced steatosis and de novo lipogenesis even in the presence of sufficient fructose and fat, demonstrating that the mechanism of voglibose could be effective in treating HFHFr diet-induced NAFLD. These results indicate that voglibose improves HFHFr diet-induced NAFLD by suppressing hepatic de novo lipogenesis.
α-葡萄糖苷酶抑制剂（α-GI）可延缓葡萄糖在肠道的吸收，从而减少餐后肝内葡萄糖摄取。这种机制被认为对治疗非酒精性脂肪性肝病（NAFLD）有效。在这里，我们研究了 α-葡萄糖苷酶抑制剂伏格列波糖对高脂肪高果糖（HFHFr）饮食诱导的 NAFLD 模型的影响。7 周龄雄性 C57BL/6J 小鼠被随机分为普通饮食组或 HFHFr 饮食组。10 周后，HFHFr 饮食组的小鼠被随机分为三组：HFHFr 饮食加载体、HFHFr 加伏格列波糖或 HFHFr 加吡格列酮。每种饮食和治疗方案均持续 10 周。HFHFr 饮食可诱导严重的非酒精性脂肪性肝病，包括脂肪变性、肝炎和纤维化。给予伏格列波糖可改善 NAFLD 的各个方面，与阳性对照吡格列酮相当。在伏格列波糖治疗的小鼠中，肝内脂肪生成标志物的基因表达显著下调。在体外实验中，减少葡萄糖向肝细胞内的流入可显著减少脂肪变性和从头脂肪生成，即使在有足够的果糖和脂肪的情况下也是如此，这表明伏格列波糖的作用机制可能对治疗 HFHFr 饮食诱导的 NAFLD 有效。这些结果表明，伏格列波糖通过抑制肝内从头脂肪生成来改善 HFHFr 饮食诱导的 NAFLD。
