PR002564 (Project)

Description:Twenty-five-week-old male mice (n=31) with diet-induced obesity were divided into four groups to investigate the impact of methionine restriction on metabolic profiles within plasma, brown adipose tissue, and liver, aiming to determine if short-term dietary methionine restriction (MetR) could reverse the metabolic disruptions caused by a high-fat diet and to characterize the resulting alterations in protein and lipid signatures across these key metabolic tissues. The control group (n=8) was maintained on a high-fat diet (HFD, 60% kcal fat/0.86% methionine) for 15 weeks, while the intervention groups were fed a modified high-fat diet with significantly reduced methionine (HFD-MetR, 60% fat/0.12% methionine) for 3 days (MetR3, n=8), 5 days (MetR5, n=8), or 10 days (MetR10, n=7), with all mice fasted for 4 hours prior to the collection of biological samples for comprehensive metabolomic analysis. Our findings revealed that even short durations of HFD-MetR led to rapid and significant metabolic improvements, evidenced by reduced circulating triglyceride levels, blood glucose, and insulin within 10 days. Furthermore, significant changes in the secretion of adipokines and hepatokines were observed, alongside distinct alterations in the overall metabolomic profiles of plasma, brown adipose tissue, and liver. Proteomic analysis of perivascular adipose tissue (PVAT) complemented these findings by revealing enriched metabolic signatures. These data demonstrate that short-term dietary methionine restriction elicits rapid and substantial changes in the metabolome across multiple tissues in obese mice, highlighting its potential as a potent dietary intervention to reverse diet-induced metabolic dysfunction.