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

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.

Keywords: MR; Methioninase; NAFLD; fatty liver; methionine restriction; mice.

MeSH terms

  • Administration, Oral
  • Animals
  • Carbon-Sulfur Lyases / administration & dosage*
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Methionine / metabolism
  • Mice
  • Non-alcoholic Fatty Liver Disease / etiology*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / prevention & control*
  • Recombinant Proteins / administration & dosage*

Substances

  • Recombinant Proteins
  • Methionine
  • Carbon-Sulfur Lyases
  • L-methionine gamma-lyase