Dietary methionine restriction improved the intestinal microbiota composition, barrier function, oxidative stress, and inflammation in high-fat-fed mice.

Dietary methionine restriction improves impairment of learning and memory function induced by obesity, likely by increasing H2S production.

Scope Dietary methionine restriction (MR) promotes multifaceted health benefits. Moreover, lower rate of protein synthesis by dietary MR is associated with life span extension. The goal of this work is to explore how dietary MR would affect protein metabolism in a mouse model of high‐fat‐diet‐induced obesity (DIO). Methods and results DIO mice (male C57BL/6) are subjected to dietary MR for 22 weeks. High‐throughput sequencing technology, qRT‐PCR analysis, and the dual luciferase reporter assay are performed to verify that MiR‐328‐3p directly targets cystathionine γ‐lyase (CSE) to modulate endogenous H2S production. Moreover, indicators of endogenous H2S, fractional synthesis rate (FSR), fractional growth rate (FGR), fractional degradation rate (FDR), and protein retention efficiency (PRE) are analyzed. MR results in an increase in endogenous H2S to relieve oxidative stress and ER stress to improve protein homeostasis and metabolic efficiency in DIO mice. Conclusion Results show that dietary MR increases endogenous H2S production via miR‐328‐3p. Furthermore, these results suggest the potential involvement of endogenous H2S on the efficiency of protein metabolism in dietary MR.