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口服重组甲硫氨酸酶可预防高脂饮食诱导的小鼠非酒精性脂肪肝病。

Oral Recombinant Methioninase Prevents Nonalcoholic Fatty Liver Disease in Mice on a High Fat Diet.

机构信息

AntiCancer Inc, San Diego, CA, U.S.A.

Department of General and Gastroenterological Surgery, Showa University School of Medicine, Tokyo, Japan.

出版信息

In Vivo. 2020 May-Jun;34(3):979-984. doi: 10.21873/invivo.11866.

Abstract

BACKGROUND/AIM: We have recently shown that oral recombinant methionase (o-rMETase) prevents obesity and diabetes onset in mice on a high-fat (HF) diet. The present study aimed to determine if o-rMETase can inhibit the onset of nonalcoholic fatty liver disease (NAFLD) onset in mice on a high-fat diet.

MATERIALS AND METHODS

Male C57BL/6J mice in the control group were fed a normal-fat diet (NFD) (+6.5% fat), and other mice were fed a high-fat (HF) diet (+34.3% fat). Then, the mice on the HF diet were divided into two dietary groups: i) HF+phosphate buffered saline (PBS) group, and ii) HF+o-rMETase group.

RESULT

The fatty change score in the livers of mice treated with HF+PBS increased to an average of 2.6 during the experimental period of 8 weeks. In contrast, the fatty change in the livers of mice on the HF+o-rMETase group had an average score of 0.92 (p=0.04, HF+PBS vs HF+o-rMETase).

CONCLUSION

o-rMETase inhibited the onset of NAFLD as well as prevented obesity and the onset of diabetes on a high-fat diet, offering a possibility of a new paradigm to prevent liver cirrhosis or liver cancer via NAFLD.

摘要

背景/目的:我们最近发现,口服重组蛋氨酸酶(o-rMETase)可预防高脂肪(HF)饮食的肥胖和糖尿病的发生。本研究旨在确定 o-rMETase 是否可以抑制高脂肪饮食的小鼠中非酒精性脂肪性肝病(NAFLD)的发生。

材料和方法

对照组雄性 C57BL/6J 小鼠喂食正常脂肪饮食(NFD)(+6.5%脂肪),其他小鼠喂食高脂肪饮食(HF)(+34.3%脂肪)。然后,将 HF 饮食组的小鼠分为两组:i)HF+磷酸盐缓冲盐水(PBS)组,ii)HF+o-rMETase 组。

结果

在 8 周的实验期间,用 HF+PBS 治疗的小鼠肝脏中的脂肪变化评分增加到平均 2.6。相比之下,HF+o-rMETase 组的小鼠肝脏中的脂肪变化平均得分为 0.92(p=0.04,HF+PBS 与 HF+o-rMETase)。

结论

o-rMETase 抑制了 NAFLD 的发生,并预防了高脂肪饮食引起的肥胖和糖尿病的发生,为通过 NAFLD 预防肝硬化或肝癌提供了一种新的范式。

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