Hepatitis C virus(HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence a...Hepatitis C virus(HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence and pathogenesis are due to the ability of HCV to deregulate specific host processes, mainly lipid metabolism and innate immunity. In particular, HCV exploits the lipoprotein machineries for almost all steps of its life cycle. The aim of this review is to summarize current knowledge concerning the interplay between HCV and lipoprotein metabolism. We discuss the role played by members of lipoproteins in HCV entry, replication and virion production.展开更多
A major obstacle in type 2 diabetes mellitus(T2DM)is sleep fragmentation(SF),which negatively affects testicular function.However,the underlying mechanisms remain to be elucidated.In this study,we demonstrate that SF ...A major obstacle in type 2 diabetes mellitus(T2DM)is sleep fragmentation(SF),which negatively affects testicular function.However,the underlying mechanisms remain to be elucidated.In this study,we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism,specifically mediated by melatonin(MEL)receptor 1a(MT1).T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis,deregulated lipid metabolism,and impaired testicular function.Unexpectedly,sleep recovery(SR)for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function.Interestingly,MEL and MT1 agonist 2-iodomelatonin(2IM)effectively improved lipid homeostasis,highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage.Mechanistically,MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1,which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF.The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout(Fgfr1-KO+/–)diabetic mice.Meanwhile,testicular-specific overexpression of Tak1 abolished the protective effect of FGF1mut on diabetic mouse testis.Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.展开更多
The lipid droplet （LD） is a unique multi-functional orga- nelle that contains a neutral lipid core covered with a phospholipid monolayer membrane. The LDs have been found in almost all organisms from bacteria to hum...The lipid droplet （LD） is a unique multi-functional orga- nelle that contains a neutral lipid core covered with a phospholipid monolayer membrane. The LDs have been found in almost all organisms from bacteria to humans with similar shape. Several conserved functions of LDs have been revealed by recent studies, including lipid metabolism and trafficking, as well as nucleic acid binding and protection. We summarized these findings and proposed a hypothesis that the LD is a conserved organelle.展开更多
In addition to white adipose tissue （WAT） that stores energy, human and small mammals also have brown adipose tissue （BAT） that dissipates chemical energy for thermogenesis. BAT contains multilocular lipid droplet...In addition to white adipose tissue （WAT） that stores energy, human and small mammals also have brown adipose tissue （BAT） that dissipates chemical energy for thermogenesis. BAT contains multilocular lipid droplets and much higher numbers of mitochondria than WAT. The mitochondria in BAT uncouple large amounts of fuel oxidation from ATP for heat generation. Accumulating evidences have demonstrated that increased activity and/or amount of BAT can reverse obesity and improve insulin resistance, which highlights that BAT plays an important role in energy metabolism. In this review, we summarized recent findings that shows advantageous effects of BAT activation in metabolic diseases. In addition, we presented the function and role of brown and beige fat cells and regulatory factors for them. Finally, we discussed the potential application of brown adipocytes-based therapy and pharmacological intervention to increase BAT activity for the treatment of obesity and related diseases including insulin resistance, cardiovascular diseases and type 2 diabetes.展开更多
基金Supported by AIRC(to Tripodi MNo.IG-13529 to Fimia GM)+6 种基金Ministry for Health of Italy(“Ricerca Corrente”to Grassi GTripodi MAlonzi TFimia GM and Ippolito G“Ricerca Finalizzata”to Fimia GM and Ippolito G)Ministry of University and Research of Italy(PRIN to Tripodi MPh D program to Di Caprio G)
文摘Hepatitis C virus(HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence and pathogenesis are due to the ability of HCV to deregulate specific host processes, mainly lipid metabolism and innate immunity. In particular, HCV exploits the lipoprotein machineries for almost all steps of its life cycle. The aim of this review is to summarize current knowledge concerning the interplay between HCV and lipoprotein metabolism. We discuss the role played by members of lipoproteins in HCV entry, replication and virion production.
基金supported by the National Natural Science Foundation of China(82272601)the Taishan Young Scholars Program(No.TSQN202306013,China).
文摘A major obstacle in type 2 diabetes mellitus(T2DM)is sleep fragmentation(SF),which negatively affects testicular function.However,the underlying mechanisms remain to be elucidated.In this study,we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism,specifically mediated by melatonin(MEL)receptor 1a(MT1).T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis,deregulated lipid metabolism,and impaired testicular function.Unexpectedly,sleep recovery(SR)for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function.Interestingly,MEL and MT1 agonist 2-iodomelatonin(2IM)effectively improved lipid homeostasis,highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage.Mechanistically,MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1,which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF.The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout(Fgfr1-KO+/–)diabetic mice.Meanwhile,testicular-specific overexpression of Tak1 abolished the protective effect of FGF1mut on diabetic mouse testis.Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.
文摘The lipid droplet （LD） is a unique multi-functional orga- nelle that contains a neutral lipid core covered with a phospholipid monolayer membrane. The LDs have been found in almost all organisms from bacteria to humans with similar shape. Several conserved functions of LDs have been revealed by recent studies, including lipid metabolism and trafficking, as well as nucleic acid binding and protection. We summarized these findings and proposed a hypothesis that the LD is a conserved organelle.
文摘In addition to white adipose tissue （WAT） that stores energy, human and small mammals also have brown adipose tissue （BAT） that dissipates chemical energy for thermogenesis. BAT contains multilocular lipid droplets and much higher numbers of mitochondria than WAT. The mitochondria in BAT uncouple large amounts of fuel oxidation from ATP for heat generation. Accumulating evidences have demonstrated that increased activity and/or amount of BAT can reverse obesity and improve insulin resistance, which highlights that BAT plays an important role in energy metabolism. In this review, we summarized recent findings that shows advantageous effects of BAT activation in metabolic diseases. In addition, we presented the function and role of brown and beige fat cells and regulatory factors for them. Finally, we discussed the potential application of brown adipocytes-based therapy and pharmacological intervention to increase BAT activity for the treatment of obesity and related diseases including insulin resistance, cardiovascular diseases and type 2 diabetes.
