Decades of international research highlight the dynamic interplay between dietary patterns and systemic metabolism.Emerging evidence underscores the central role of sphingolipids and their metabolic pathways in regula...Decades of international research highlight the dynamic interplay between dietary patterns and systemic metabolism.Emerging evidence underscores the central role of sphingolipids and their metabolic pathways in regulating diverse physiological processes.However,the links between specific diets,sphingolipidomic remodeling,and metabolic outcomes remain underexplored.This study employed transcriptomic and sphingo-lipidomic analyses to profile diet-specific sphingolipid signatures and metabolic alterations in the liver,serum,and hypothalamus of mice fed Mediterranean(MD),ketogenic(KD),intermittent fasting(IF),or Western(WD)diets,with standard chow(CD)as the control group.Notably,substantial remodeling of sphingolipid metabolism was observed across dietary interventions,particularly in the salvage and de novo synthesis pathways.The MD and KD groups revealed reduced hepatic and serum levels of pro-inflammatory long-chain ceramides,e.g.,Cer(d18:1/16:0),Cer(d18:1/18:0),while increasing cardioprotective ultra-long-chain ceramides,e.g.,Cer(d18:1/26:0).In contrast,WD was associated with widespread ceramide accumulation in these tissues,along with upregulation of DEGS1/2.IF and WD uniquely enriched 1-deoxyceramides,e.g.,1-deoxyCer(m18:0/16:0),lipids associated with metabolic dysfunction.Given the role of the hypothalamus in metabolic regulation,its tran-scriptome analysis revealed diet-specific modulation of sphingolipid-related genes.Taken together,MD and KD emerged as favorable dietary patterns for restoring sphingolipid homeostasis,whereas WD exacerbated patho-logical lipid signatures.This study provides a resource for clarifying potential mechanistic links between dietary patterns and lipid metabolism,offering insights into metabolic disease prevention.展开更多
Cordyceps is a precious Chinese medicine with various pharmacological activities.In 1995,a potent immunosuppressive active sphingolipid named myriocin was isolated from the culture broth of Isaria sinclairii.FTY720,a ...Cordyceps is a precious Chinese medicine with various pharmacological activities.In 1995,a potent immunosuppressive active sphingolipid named myriocin was isolated from the culture broth of Isaria sinclairii.FTY720,a sphingolipid analogue modified from myriocin,has been developed into an important oral drug for the treatment of multiple sclerosis and organ transplantation.展开更多
基金supported by the Youth Cross-innovation Research Program of CFSE-OUC(No.2024104)Youth Talent Project Launch Fund of Ocean University of China(No.862401013170)Post-doctoral Fellowship Program of CPSF(No.GZB20240695).
文摘Decades of international research highlight the dynamic interplay between dietary patterns and systemic metabolism.Emerging evidence underscores the central role of sphingolipids and their metabolic pathways in regulating diverse physiological processes.However,the links between specific diets,sphingolipidomic remodeling,and metabolic outcomes remain underexplored.This study employed transcriptomic and sphingo-lipidomic analyses to profile diet-specific sphingolipid signatures and metabolic alterations in the liver,serum,and hypothalamus of mice fed Mediterranean(MD),ketogenic(KD),intermittent fasting(IF),or Western(WD)diets,with standard chow(CD)as the control group.Notably,substantial remodeling of sphingolipid metabolism was observed across dietary interventions,particularly in the salvage and de novo synthesis pathways.The MD and KD groups revealed reduced hepatic and serum levels of pro-inflammatory long-chain ceramides,e.g.,Cer(d18:1/16:0),Cer(d18:1/18:0),while increasing cardioprotective ultra-long-chain ceramides,e.g.,Cer(d18:1/26:0).In contrast,WD was associated with widespread ceramide accumulation in these tissues,along with upregulation of DEGS1/2.IF and WD uniquely enriched 1-deoxyceramides,e.g.,1-deoxyCer(m18:0/16:0),lipids associated with metabolic dysfunction.Given the role of the hypothalamus in metabolic regulation,its tran-scriptome analysis revealed diet-specific modulation of sphingolipid-related genes.Taken together,MD and KD emerged as favorable dietary patterns for restoring sphingolipid homeostasis,whereas WD exacerbated patho-logical lipid signatures.This study provides a resource for clarifying potential mechanistic links between dietary patterns and lipid metabolism,offering insights into metabolic disease prevention.
文摘Cordyceps is a precious Chinese medicine with various pharmacological activities.In 1995,a potent immunosuppressive active sphingolipid named myriocin was isolated from the culture broth of Isaria sinclairii.FTY720,a sphingolipid analogue modified from myriocin,has been developed into an important oral drug for the treatment of multiple sclerosis and organ transplantation.
