Diet interventions such as calorie restriction or time-restricted feeding offer potential for weight management,but long-term success is often hindered by poor adherence due to the rewarding effects of sugars.In this ...Diet interventions such as calorie restriction or time-restricted feeding offer potential for weight management,but long-term success is often hindered by poor adherence due to the rewarding effects of sugars.In this study,we demonstrate that sulfur amino acid restriction(SAAR)diets promote rapid fat loss without impairing appetite and physiological locomotion,outperforming diets with restricted branched-chain amino acids.Weekly cycling of SAAR diets preserves metabolic benefits,such as reduced fat mass and improved glucose sensitivity.Metabolic analysis and in vivo isotope tracing revealed a shift toward carbohydrate oxidation in white and brown adipose tissue(WAT and BAT),and liver during the SAAR diet refeeding state,leading to decreased de novo lipogenesis.Enhanced lipolysis and fatty acid oxidation were observed in the heart,brain,BAT,lungs,etc.The reintroduction of methionine or cystine negated these metabolic benefits.Further 13C and 2H tracing experiments indicated that cystine,rather than its derivatives like taurine or H2S,directly regulates adiposity.In a high-fat diet model,SAAR diet led to sustained fat mass reduction,regardless of the timing of intervention.Additionally,cystine levels correlated positively with body mass index(BMI)and total triglycerides in diabetic patients.Our findings highlight SAAR diet as a promising strategy for long-term weight control by modulating systemic glucose and lipid metabolism homeostasis.展开更多
基金supported by grants from the National Science Foundation of China(32271354 to L.Y.)the National Key R&D Program of China(2022YFA1305200 to L.Y.)+3 种基金the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2021-RC350-008 to L.W.)the Talent Plan of Shanghai Branch-Chinese Academy of Sciences(CASSHB-QNPD-2023-011 to L.Y.)the State Key Laboratory Special Fund(2060204 to L.W.)the Beijing Natural Science Foundation(Z240014 to L.W.)。
文摘Diet interventions such as calorie restriction or time-restricted feeding offer potential for weight management,but long-term success is often hindered by poor adherence due to the rewarding effects of sugars.In this study,we demonstrate that sulfur amino acid restriction(SAAR)diets promote rapid fat loss without impairing appetite and physiological locomotion,outperforming diets with restricted branched-chain amino acids.Weekly cycling of SAAR diets preserves metabolic benefits,such as reduced fat mass and improved glucose sensitivity.Metabolic analysis and in vivo isotope tracing revealed a shift toward carbohydrate oxidation in white and brown adipose tissue(WAT and BAT),and liver during the SAAR diet refeeding state,leading to decreased de novo lipogenesis.Enhanced lipolysis and fatty acid oxidation were observed in the heart,brain,BAT,lungs,etc.The reintroduction of methionine or cystine negated these metabolic benefits.Further 13C and 2H tracing experiments indicated that cystine,rather than its derivatives like taurine or H2S,directly regulates adiposity.In a high-fat diet model,SAAR diet led to sustained fat mass reduction,regardless of the timing of intervention.Additionally,cystine levels correlated positively with body mass index(BMI)and total triglycerides in diabetic patients.Our findings highlight SAAR diet as a promising strategy for long-term weight control by modulating systemic glucose and lipid metabolism homeostasis.
