Methionine restriction decreases fat mass in C57BL/6 mice via increasing endogenous hydrogen sulfide production

Abstract

Dietary methionine restriction (MR) increases lifespan, reduces adiposity in diverse organisms. However, the mechanisms underlying the healthy benefits of adiposity reduction remain largely unknown. This study aimed to investigate the effects of MR on the activity of the transsulfuration pathway (TSP) enzyme cystathionine γ‐lyase (CGL), hydrogen sulfide (H2S) production, and lipid metabolism in high‐fat diet mice. C57BL/6 mice were fed a high fat diet (HFD) containing either 0.86% methionine (CF) or 0.17% methionine (MR). In the 23th week, lipid profiles, the activity of CGL and the level of H2S in liver were determined. The mRNA level of CGL and the relactive genes (FAS, ACC‐1, SREBP1c, CYP7A1, CPT1 and PPARα) expression of lipid metabolism in mice liver were assayed by real‐time PCR. The protein level of CGL was measured by western blot. We found that compared with CF group, MR significantly decreased the level of triglyceride and cholesterol in mice plasma. The fat synthesis genes (FAS, ACC‐1 and SREBP1c) of MR group were down‐regulated and the fatty acid oxidation genes (CYP7A1, CPT1 and PPARα) were increased. And we found MR significantly increased mRNA and protein expression of CGL, and increased H2S production in mice liver. We concluded that MR can attenuate high‐fat diet‐induced adiposity possibly through increasing endogenous H2S production.Support or Funding InformationThis research was supported by program of “Collaborative innovation center of food safety and quality control in Jiangsu Province”, the National Natural Science Foundation of China (No. 31571841), State Key Laboratory of Food Science and Technology of Jiangnan University in China (SKLF‐ZZB‐201609), and China Postdoctoral Science Foundation (2015M571669).