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

Abstract

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.

Circular RNA hsa_circRNA_002178 silencing retards breast cancer progression via microRNA‐328‐3p‐mediated inhibition of COL1A1

“…This study provided evidence that miR-328-3p was lowly expressed in clinical breast cancer tissues. 27 It was also suggested that hsa_circRNA_002178 positively regulated the expression of COL1A1 via sponging miR-328-3p. 26 Consistently, transfection with miR-328-3p mimic in breast cancer cells leads to lowered cell motility.…”

“…13 miR-328-3p was also involved in the regulation of liver protein metabolism mediated by protein homeostasis and metabolic efficiency. 27 It was also suggested that hsa_circRNA_002178 positively regulated the expression of COL1A1 via sponging miR-328-3p. Recently, it has been reported that circRNAs in mammals are able to act as sponges or competing endogenous RNA (ceRNAs) of miRs thus affecting its transcriptional control.…”

Protein, amino acids and obesity treatment

“…In DIO mice models, methionine restriction also improves lipid profiles and hepatosteatosis [56,88,90,93,94]. Methionine restriction reduced the lipogenesis/lipid catabolism ratio, improving lipid accumulation and thus liver function, in male C57BL/6 J mice fed a 21 week long HFD [56].…”

“…Firstly, restricting methionine in C57BL/6 J mice fed a 10 week long HFD lowered pro-inflammatory cytokine levels while raising anti-inflammatory cytokine rates in plasma and hippocampus, compared to mice without restriction [88]. Secondly, methionine restriction affects the oxidative stress balance in the liver by upregulating transsulfuration pathways of methionine, increasing H2S plasmatic levels [56,93]. Indeed, the transsulfuration pathway after methionine catabolism leads to converting homocysteine to cysteine, producing H2S as a byproduct when degrading homocysteine or cysteine further [97].…”

Dietary methionine restriction attenuates renal ischaemia/reperfusion‐induced myocardial injury by activating the CSE/H2S/ERS pathway in diabetic mice

“…49 Therefore, there is a close correlation between the level of ERS and the apoptosis of myocardiocytes. Other studies demonstrated that an excessive level of ERS can be induced by certain factors, including ischaemia andhypoxia, which subsequently induces the death of myocardiocytes via the signalling pathways of JNK, caspase-12 and CHOP 22,23,50.…”