Fat-1,an enzyme encoded by the fat-1 gene,is responsible for the conversion of endogenous omega-6 polyunsaturated fatty acids into omega-3 polyunsaturated fatty acids in Caenorhabditis elegans.To better investigate wh...Fat-1,an enzyme encoded by the fat-1 gene,is responsible for the conversion of endogenous omega-6 polyunsaturated fatty acids into omega-3 polyunsaturated fatty acids in Caenorhabditis elegans.To better investigate whether the expression of Fat-1 will exert a beneficial function in dyslipidemia and metabolic dysfunction-associated fatty liver disease(MAFLD),we established an adeno-associated virus 9 expressing Fat-1.We found that adeno-associated-virus-mediated expression of Fat-1 markedly reduced the levels of plasma triglycerides and total cholesterol but increased high-density lipoprotein levels in male wild-type hamsters on both chow diet and high-fat diet as well as in chow-diet-fed male LDLR^(-/-)hamsters.Fat-1 ameliorated diet-induced MAFLD in wild-type hamsters by enhancing fatty acid oxidation through the hepatic peroxisome proliferator-activated receptorα(PPARα)-dependent pathway.Mechanistically,Fat-1 increased the levels of multiple lipid derivatives as ligands for PPARα and simultaneously facilitated the nuclear localization of PPARα.Our results provide new insights into the multiple therapeutic potentials of Fat-1 to treat dyslipidemia,MAFLD,and atherosclerosis.展开更多
Cardiovascular disease is the leading cause of morbidity and mortality in both developed and developing countries,in which atherosclerosis triggered by dyslipidemia is the major pathological basis.Over the past 40 yea...Cardiovascular disease is the leading cause of morbidity and mortality in both developed and developing countries,in which atherosclerosis triggered by dyslipidemia is the major pathological basis.Over the past 40 years,small rodent animals,such as mice,have been widely used for understanding of human atherosclerosis-related cardiovascular disease(ASCVD)with the advantages of low cost and ease of maintenance and manipulation.However,based on the concept of precision medicine and high demand of translational research,the applications of mouse models for human ASCVD study would be limited due to the natural differences in metabolic features between mice and humans even though they are still the most powerful tools in this research field,indicating that other species with biological similarity to humans need to be considered for studying ASCVD in future.With the development and breakthrough of novel gene editing technology,Syrian golden hamster,a small rodent animal replicating the metabolic characteristics of humans,has been genetically modified,suggesting that gene-targeted hamster models will provide new insights into the precision medicine and translational research of ASCVD.The purpose of this review was to summarize the genetically-modified hamster models with dyslipidemia to date,and their potential applications and perspective for ASCVD.展开更多
Combined hyperlipidemia(CHL)manifests as elevated cholesterol and triglycerides,associated with fatty liver and cardiovascular diseases.Emerging evidence underscores the crucial role of the intestinal microbiota in me...Combined hyperlipidemia(CHL)manifests as elevated cholesterol and triglycerides,associated with fatty liver and cardiovascular diseases.Emerging evidence underscores the crucial role of the intestinal microbiota in metabolic disorders.However,the potential therapeutic viability of remodeling the intestinal microbiota in CHL remains uncertain.In this study,CHL was induced in low-density lipoprotein receptordeficient(LDLR^(-/-))hamsters through an 8-week high-fat and high-cholesterol(HFHC)diet or a 4-month high-cholesterol(HC)diet.展开更多
基金supported by the National Natural Science Foundation of China(NSFC)82270479,82070460,and HY2021-1 to Xunde Xianthe Beijing Natural Science Foundation 7242084 to Xunde Xian+1 种基金the Fundamental Research Funds for the Central Universities to Xunde XianPeking University Medicine plus X Pilot Program-Platform Construction Project 2024YXXLHPT010 to Xunde Xian.
文摘Fat-1,an enzyme encoded by the fat-1 gene,is responsible for the conversion of endogenous omega-6 polyunsaturated fatty acids into omega-3 polyunsaturated fatty acids in Caenorhabditis elegans.To better investigate whether the expression of Fat-1 will exert a beneficial function in dyslipidemia and metabolic dysfunction-associated fatty liver disease(MAFLD),we established an adeno-associated virus 9 expressing Fat-1.We found that adeno-associated-virus-mediated expression of Fat-1 markedly reduced the levels of plasma triglycerides and total cholesterol but increased high-density lipoprotein levels in male wild-type hamsters on both chow diet and high-fat diet as well as in chow-diet-fed male LDLR^(-/-)hamsters.Fat-1 ameliorated diet-induced MAFLD in wild-type hamsters by enhancing fatty acid oxidation through the hepatic peroxisome proliferator-activated receptorα(PPARα)-dependent pathway.Mechanistically,Fat-1 increased the levels of multiple lipid derivatives as ligands for PPARα and simultaneously facilitated the nuclear localization of PPARα.Our results provide new insights into the multiple therapeutic potentials of Fat-1 to treat dyslipidemia,MAFLD,and atherosclerosis.
基金supported by National Natural Science Foundation of China NSFC 31520103909 and 91739105 to G.L.,81770449 to Y.W.and 82070460 to X.X.Peking University BMU2020MX001 and BMU2020XY011 to X.X.G.L.
文摘Cardiovascular disease is the leading cause of morbidity and mortality in both developed and developing countries,in which atherosclerosis triggered by dyslipidemia is the major pathological basis.Over the past 40 years,small rodent animals,such as mice,have been widely used for understanding of human atherosclerosis-related cardiovascular disease(ASCVD)with the advantages of low cost and ease of maintenance and manipulation.However,based on the concept of precision medicine and high demand of translational research,the applications of mouse models for human ASCVD study would be limited due to the natural differences in metabolic features between mice and humans even though they are still the most powerful tools in this research field,indicating that other species with biological similarity to humans need to be considered for studying ASCVD in future.With the development and breakthrough of novel gene editing technology,Syrian golden hamster,a small rodent animal replicating the metabolic characteristics of humans,has been genetically modified,suggesting that gene-targeted hamster models will provide new insights into the precision medicine and translational research of ASCVD.The purpose of this review was to summarize the genetically-modified hamster models with dyslipidemia to date,and their potential applications and perspective for ASCVD.
基金supported by the National Natural Science Foundation of China(NSFC)82070460,82270479,and HY2021-1 to X.Xthe Fundamental Research Funds for the Central Universities to X.X.
文摘Combined hyperlipidemia(CHL)manifests as elevated cholesterol and triglycerides,associated with fatty liver and cardiovascular diseases.Emerging evidence underscores the crucial role of the intestinal microbiota in metabolic disorders.However,the potential therapeutic viability of remodeling the intestinal microbiota in CHL remains uncertain.In this study,CHL was induced in low-density lipoprotein receptordeficient(LDLR^(-/-))hamsters through an 8-week high-fat and high-cholesterol(HFHC)diet or a 4-month high-cholesterol(HC)diet.
