Methionine restriction observed to reverse old-age obesity in mice

by Impact Journals LLC

Blood methionine level at day 15 (A) and day 29 (B). Credit: 2023 Kubota et al

Obesity increases with aging. Methionine restriction affects lipid metabolism and can prevent obesity in mice. In a new study published in the journal Aging, researchers from AntiCancer Inc., University of California San Diego and Showa University School of Medicine observed C57BL/6 mice double their body weight from 4 to 48 weeks of age and become obese. The team then evaluated the efficacy of oral administration of recombinant-methioninase (rMETase)-producing E. coli (E. coli JM109-rMETase) or a methionine-deficient diet to reverse old-age-induced obesity in C57BL/6 mice.

“In the present study we tested a low-methionine diet to reverse old-age-induced obesity. […] E. coli JM109-rMETase was also tested in the present study to reverse old-age-induced obesity,” state the researchers.

Fifteen C57BL/6 male mice aged 12–18 months with old-age-induced obesity were divided into three groups. Group 1 was given a normal diet supplemented with non-recombinant E. coli JM109 cells orally by gavage twice daily; Group 2 was given a normal diet supplemented with recombinant E. coli JM109-rMETase cells by gavage twice daily; and Group 3 was given a methionine-deficient diet without treatment.

The administration of E. coli JM109-rMETase or a methionine-deficient diet reduced the blood methionine level and reversed old-age-induced obesity with significant weight loss by 14 days. There was a negative correlation between methionine levels and negative body weight change. Although the degree of efficacy was higher in the methionine-deficient diet group than in the E. coli JM109-rMETase group, the present findings suggested that oral administration of E. coli JM109-rMETase, as well as a methionine-deficient diet, are effective in reversing old-age-induced obesity.

“In conclusion, the present study provides evidence that restricting methionine by either a low-methionine diet or E. coli JM109-rMETase has clinical potential to treat old-age-induced obesity,” say the researchers.