Mucopolysaccharidoses(MPS)are a group of rare inborn errors of metabolism caused by defective lysosomal enzymes which prevent cells from degrading and recycling certain carbohydrates and fats,resulting in the storage ...Mucopolysaccharidoses(MPS)are a group of rare inborn errors of metabolism caused by defective lysosomal enzymes which prevent cells from degrading and recycling certain carbohydrates and fats,resulting in the storage of glycosaminoglycans in cells throughout the body.This leads to multisystem abnormalities involving bone,connective tissues,brain,blood,spinal cord,skin,and other tissues.展开更多
Immunometabolism,which is the metabolic reprogramming of anaerobic glycolysis,oxidative phosphorylation,and metabolite synthesis upon immune cell activation,has gained importance as a regulator of the homeostasis,acti...Immunometabolism,which is the metabolic reprogramming of anaerobic glycolysis,oxidative phosphorylation,and metabolite synthesis upon immune cell activation,has gained importance as a regulator of the homeostasis,activation,proliferation,and differentiation of innate and adaptive immune cell subsets that function as key factors in immunity.Metabolic changes in epithelial and other stromal cells in response to different stimulatory signals are also crucial in infection,inflammation,cancer,autoimmune diseases,and metabolic disorders.The crosstalk between the PI3K-AKT-mTOR and LKB1-AMPK signaling pathways is critical for modulating both immune and nonimmune cell metabolism.The bidirectional interaction between immune cells and metabolism is a topic of intense study.Toll-like receptors(TLRs),cytokine receptors,and T and B cell receptors have been shown to activate multiple downstream metabolic pathways.However,how intracellular innate immune sensors/receptors intersect with metabolic pathways is less well understood.The goal of this review is to examine the link between immunometabolism and the functions of several intracellular innate immune sensors or receptors,such as nucleotide-binding and leucine-rich repeat-containing receptors(NLRs,or NOD-like receptors),absent in melanoma 2(AIM2)-like receptors(ALRs),and the cyclic dinucleotide receptor stimulator of interferon genes(STING).We will focus on recent advances and describe the impact of these intracellular innate immune receptors on multiple metabolic pathways.Whenever appropriate,this review will provide a brief contextual connection to pathogenic infections,autoimmune diseases,cancers,metabolic disorders,and/or inflammatory bowel diseases.展开更多
Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues,which contribute to devastating diseases such as cardiovascular diseases,stroke and cancers.The brain plays a ce...Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues,which contribute to devastating diseases such as cardiovascular diseases,stroke and cancers.The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs,sends regulatory projections and orchestrates the whole-body function.Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions.This review highlights brain dysfunction linked to genetic mutations,sex,brain inflammation,microbiota,stress as causes for whole-body pathophysiology,arguing brain dysfunction as a root cause for the epidemic of aging and obesity-related disorders.We also speculate key issues that need to be addressed on how to reveal relevant brain dysfunction that underlines the development of these disorders and diseases in order to develop new treatment strategies against these health problems.展开更多
Diederick J.van Doorn1,Adriaan G.Holleboom2,R.Bart Takkenberg1,Joanne Verheij3,Marten A.Lantinga11Department of Gastroenterology and Hepatology,Amsterdam UMC,University of Amsterdam,Amsterdam Gastroenterology Endocrin...Diederick J.van Doorn1,Adriaan G.Holleboom2,R.Bart Takkenberg1,Joanne Verheij3,Marten A.Lantinga11Department of Gastroenterology and Hepatology,Amsterdam UMC,University of Amsterdam,Amsterdam Gastroenterology Endocrinology Metabolism,Amsterdam,The Netherlands;2Department of Vascular Medicine,Internal Medicine,Amsterdam UMC,University of Amsterdam,Amsterdam Gastroenterology Endocrinology Metabolism,Amsterdam,The Netherlands;3Department of Hepatopanc Metabolic dysfunction-associated steatotic liver disease(MASLD)-until recently termed non-alcoholic fatty liver disease(NAFLD)-is a rising cause of chronic liver disease with an estimated global prevalence of 30%(1).展开更多
文摘Mucopolysaccharidoses(MPS)are a group of rare inborn errors of metabolism caused by defective lysosomal enzymes which prevent cells from degrading and recycling certain carbohydrates and fats,resulting in the storage of glycosaminoglycans in cells throughout the body.This leads to multisystem abnormalities involving bone,connective tissues,brain,blood,spinal cord,skin,and other tissues.
基金The following funding supports are acknowledged:NIH(R35 CA232109,PO1 DK094779,U19 AI067798,R01 AI141333,and R01 AI029564).
文摘Immunometabolism,which is the metabolic reprogramming of anaerobic glycolysis,oxidative phosphorylation,and metabolite synthesis upon immune cell activation,has gained importance as a regulator of the homeostasis,activation,proliferation,and differentiation of innate and adaptive immune cell subsets that function as key factors in immunity.Metabolic changes in epithelial and other stromal cells in response to different stimulatory signals are also crucial in infection,inflammation,cancer,autoimmune diseases,and metabolic disorders.The crosstalk between the PI3K-AKT-mTOR and LKB1-AMPK signaling pathways is critical for modulating both immune and nonimmune cell metabolism.The bidirectional interaction between immune cells and metabolism is a topic of intense study.Toll-like receptors(TLRs),cytokine receptors,and T and B cell receptors have been shown to activate multiple downstream metabolic pathways.However,how intracellular innate immune sensors/receptors intersect with metabolic pathways is less well understood.The goal of this review is to examine the link between immunometabolism and the functions of several intracellular innate immune sensors or receptors,such as nucleotide-binding and leucine-rich repeat-containing receptors(NLRs,or NOD-like receptors),absent in melanoma 2(AIM2)-like receptors(ALRs),and the cyclic dinucleotide receptor stimulator of interferon genes(STING).We will focus on recent advances and describe the impact of these intracellular innate immune receptors on multiple metabolic pathways.Whenever appropriate,this review will provide a brief contextual connection to pathogenic infections,autoimmune diseases,cancers,metabolic disorders,and/or inflammatory bowel diseases.
基金the National Key R&D Program of China(2019YFA0801900,2018YFA0800300)the National Natural Science Foundation of China(91749104 and 31971074)+2 种基金the Science and Technology Innovation Action Plan of Shanghai Science and Technology Committee(18140901300)the Open Research Fund of the National Key Laboratory of Genetic Engineering(SKLGE1803)the Shanghai Pujiang Talent Project(18PJ1400700)to T.L.,and Dr.Tong is the holder of Cullen Chair in Molecular Medicine at McGovern Medical School of UTHealth.
文摘Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues,which contribute to devastating diseases such as cardiovascular diseases,stroke and cancers.The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs,sends regulatory projections and orchestrates the whole-body function.Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions.This review highlights brain dysfunction linked to genetic mutations,sex,brain inflammation,microbiota,stress as causes for whole-body pathophysiology,arguing brain dysfunction as a root cause for the epidemic of aging and obesity-related disorders.We also speculate key issues that need to be addressed on how to reveal relevant brain dysfunction that underlines the development of these disorders and diseases in order to develop new treatment strategies against these health problems.
文摘Diederick J.van Doorn1,Adriaan G.Holleboom2,R.Bart Takkenberg1,Joanne Verheij3,Marten A.Lantinga11Department of Gastroenterology and Hepatology,Amsterdam UMC,University of Amsterdam,Amsterdam Gastroenterology Endocrinology Metabolism,Amsterdam,The Netherlands;2Department of Vascular Medicine,Internal Medicine,Amsterdam UMC,University of Amsterdam,Amsterdam Gastroenterology Endocrinology Metabolism,Amsterdam,The Netherlands;3Department of Hepatopanc Metabolic dysfunction-associated steatotic liver disease(MASLD)-until recently termed non-alcoholic fatty liver disease(NAFLD)-is a rising cause of chronic liver disease with an estimated global prevalence of 30%(1).
