Dietary Methionine Restriction Upregulates Endogenous H2S via miR‐328‐3p: A Potential Mechanism to Improve Liver Protein Metabolism Efficiency in a Mouse Model of High‐fat‐diet‐induced Obesity

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 H2 S production. Moreover, indicators of endogenous H2 S, 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 H2 S 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 H2 S production via miR-328-3p. Furthermore, these results suggest the potential involvement of endogenous H2 S on the efficiency of protein metabolism in dietary MR.