Methionine restriction plus overload improves skeletal muscle and metabolic health in old mice on a high fat diet

Abstract

Methionine restriction (MR) has been shown to reduce the age-induced inflammation. We examined the effect of MR (0.17% methionine, 10% kCal fat) and MR + high fat diet (HFD) (0.17% methionine, 45% kCal fat) on body mass, food intake, glucose tolerance, resting energy expenditure, hind limb muscle mass, denervation-induced atrophy and overload-induced hypertrophy in young and old mice. In old mice, MR and MR + HFD induced a decrease in body mass. Muscle mass per body mass was lower in old compared to young mice. MR restored some of the HFD-induced reduction in muscle oxidative capacity. The denervation-induced atrophy of the m. gastrocnemius was larger in animals on MR than on a control diet, irrespective of age. Old mice on MR had larger hypertrophy of m. plantaris. Irrespective of age, MR and MR + HFD had better glucose tolerance compared to the other groups. Young and old mice on MR + HFD had a higher resting VO2 per body mass than HFD group. Mice on MR and MR + HFD had a resting respiratory quotient closer to 0.70, irrespective of age, indicating an increased utilization of lipids. In conclusion, MR in combination with resistance training may improve skeletal muscle and metabolic health in old age even in the face of obesity.

Metabolic benefits of methionine restriction in adult mice do not require functional methionine sulfoxide reductase A (MsrA)

“…2 h). A similar decrease in mass has been reported in other MR studies 4 , 7 , 47 . Further examination of muscle function and structure will be necessary to delineate this potential novel relationship between methionine metabolism and muscle.…”

Metabolic Benefits of Methionine Restriction in Adult Mice Do Not Require Functional Methionine Sulfoxide Reductase a (MsrA)

“…2h). A similar decrease in mass has been reported in other MR studies [4,7,47] . Further examination of muscle function and structure will be necessary to delineate this potential novel relationship between methionine metabolism and muscle.…”

“…Previous studies have shown that dietary methionine restriction (MR) in rodents can extend lifespan up to 42% compared to rodents fed diets replete with methionine [1][2][3] . Moreover, MR has strong effects on metabolic function and has been shown to improve glucose homeostasis [4][5][6][7][8][9] , decrease oxidative stress [2,[10][11][12][13][14][15] , and promote adipose tissue browning [16][17][18][19][20][21][22] . These findings are consistent with the idea that dietary intervention by restricting methionine improves health in addition to extending longevity.…”

Skeletal muscle and fiber type-specific intramyocellular lipid accumulation in obese mice

“…However, as any other rodent model, it has its limitations in recapitulating all the hallmarks of the complex disease in humans [ 47 ]. Our study was also performed only in female mice, and given that sex differences in insulin sensitivity have been reported in rat and mouse models, it would be important in future experiments to also explore the same study design in male mice [ 48 - 50 ].…”