GULP1是一种含磷酸化酪氨酸结合(phosphotyrosine-binding,PTB)结构域的吞噬衔接蛋白,已有的研究表明它可促进脂肪细胞3T3-L1的糖摄取。为进一步挖掘GULP1下游关键的代谢相关差异基因,本研究对过表达GULP1的脂肪细胞和骨骼肌细胞进行转...GULP1是一种含磷酸化酪氨酸结合(phosphotyrosine-binding,PTB)结构域的吞噬衔接蛋白,已有的研究表明它可促进脂肪细胞3T3-L1的糖摄取。为进一步挖掘GULP1下游关键的代谢相关差异基因,本研究对过表达GULP1的脂肪细胞和骨骼肌细胞进行转录组分析,然后对表达异常基因进行生物信息学分析,并通过实时荧光定量PCR(real-time fluorescent quantitative PCR,qRT-PCR)与转录组测序进行相互验证。结果表明:以P<0.05和|Log_(2)Foldchange|≥1为阈值筛选差异表达基因,发现与对照细胞相比,过表达GULP1的脂肪细胞中有278个上调基因和263个下调基因,与代谢相关的GO(Gene Ontology)条目包括胆固醇生物合成过程、胆固醇代谢过程、对脂多糖的反应、脂质代谢过程等,有52个代谢相关差异表达基因富集到10条KEGG(Kyoto Encyclopedia of Genes and Genomes)通路,其中脂质代谢被高度富集;过表达GULP1的骨骼肌细胞有280个上调基因和302个下调基因,与代谢相关的GO条目包括激素代谢过程、对脂多糖的反应、单碳代谢过程等,有86个代谢相关差异表达基因富集到10条KEGG通路,其中氨基酸代谢、脂质代谢、碳水化合物代谢被高度富集。GULP1的生物学功能涉及广泛,包括脂代谢、肿瘤等方面。本研究通过转录组学以及生物信息学分析,筛选出GULP1下游关键的代谢相关差异基因,获得了过表达GULP1后的代谢相关差异基因及信号通路,为今后GULP1下游靶基因的研究提供了重要的理论依据。展开更多
Dysregulation of microRNA(miRNA)expression following the development of obesity is closely linked to the onset of type 2 diabetes mellitus(T2DM).Identifying differentially expressed miRNAs and their roles in regulatin...Dysregulation of microRNA(miRNA)expression following the development of obesity is closely linked to the onset of type 2 diabetes mellitus(T2DM).Identifying differentially expressed miRNAs and their roles in regulating glucose metabolism will provide a theoretical foundation for the molecular mechanisms underlying obesity-induced T2DM.Here,we perform a genome-wide association study involving 5 glycolipid metabolism traits in 1783 Kazakh and 1198 Uyghur individuals to identify miRNAs associated with fasting plasma glucose(FPG)levels.A miR-548ab mimic and inhibitor are administered to hepatocytes and adipocytes,as well as obese and diabetic mice,to determine miR-548ab-related downstream signalling pathways.The effects of miR-548ab on glucose metabolism are validated using the glucose tolerance test and insulin tolerance test.Collectively,these results indicate that miR-548ab is significantly associated with FPG levels and obesity-related T2DM in both Kazakh and Uyghur populations.The miR-548ab-GULP1/SLC25A21-GLUT4 network exerts regulatory effects on glucose metabolism,obesity,and T2DM,positioning it as a candidate risk factor,potential diagnostic marker,and therapeutic target for obesity-induced T2DM.Additionally,through evolutionary analysis,the authentic variants or haplotypes of GULP1 and SLC25A21 are categorized according to their genetic susceptibility to T2DM.The miR-548ab inhibitor shows beneficial effects in obese and diabetic mice.展开更多
文摘GULP1是一种含磷酸化酪氨酸结合(phosphotyrosine-binding,PTB)结构域的吞噬衔接蛋白,已有的研究表明它可促进脂肪细胞3T3-L1的糖摄取。为进一步挖掘GULP1下游关键的代谢相关差异基因,本研究对过表达GULP1的脂肪细胞和骨骼肌细胞进行转录组分析,然后对表达异常基因进行生物信息学分析,并通过实时荧光定量PCR(real-time fluorescent quantitative PCR,qRT-PCR)与转录组测序进行相互验证。结果表明:以P<0.05和|Log_(2)Foldchange|≥1为阈值筛选差异表达基因,发现与对照细胞相比,过表达GULP1的脂肪细胞中有278个上调基因和263个下调基因,与代谢相关的GO(Gene Ontology)条目包括胆固醇生物合成过程、胆固醇代谢过程、对脂多糖的反应、脂质代谢过程等,有52个代谢相关差异表达基因富集到10条KEGG(Kyoto Encyclopedia of Genes and Genomes)通路,其中脂质代谢被高度富集;过表达GULP1的骨骼肌细胞有280个上调基因和302个下调基因,与代谢相关的GO条目包括激素代谢过程、对脂多糖的反应、单碳代谢过程等,有86个代谢相关差异表达基因富集到10条KEGG通路,其中氨基酸代谢、脂质代谢、碳水化合物代谢被高度富集。GULP1的生物学功能涉及广泛,包括脂代谢、肿瘤等方面。本研究通过转录组学以及生物信息学分析,筛选出GULP1下游关键的代谢相关差异基因,获得了过表达GULP1后的代谢相关差异基因及信号通路,为今后GULP1下游靶基因的研究提供了重要的理论依据。
基金supported by the Natural Science Foundation of China(82160156,82260162,and 32370669)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38040200)+1 种基金the Tianshan Talent Project in Xinjiang Autonomous Region(2023TSYCCX0116 and 2023TSYCQNTJ0032)the Scientific and Technological Research Project of Xinjiang Production and Construction Corps(2022ZD001,2021AB028,2022AB022,2023AB057,and 2023ZD037).
文摘Dysregulation of microRNA(miRNA)expression following the development of obesity is closely linked to the onset of type 2 diabetes mellitus(T2DM).Identifying differentially expressed miRNAs and their roles in regulating glucose metabolism will provide a theoretical foundation for the molecular mechanisms underlying obesity-induced T2DM.Here,we perform a genome-wide association study involving 5 glycolipid metabolism traits in 1783 Kazakh and 1198 Uyghur individuals to identify miRNAs associated with fasting plasma glucose(FPG)levels.A miR-548ab mimic and inhibitor are administered to hepatocytes and adipocytes,as well as obese and diabetic mice,to determine miR-548ab-related downstream signalling pathways.The effects of miR-548ab on glucose metabolism are validated using the glucose tolerance test and insulin tolerance test.Collectively,these results indicate that miR-548ab is significantly associated with FPG levels and obesity-related T2DM in both Kazakh and Uyghur populations.The miR-548ab-GULP1/SLC25A21-GLUT4 network exerts regulatory effects on glucose metabolism,obesity,and T2DM,positioning it as a candidate risk factor,potential diagnostic marker,and therapeutic target for obesity-induced T2DM.Additionally,through evolutionary analysis,the authentic variants or haplotypes of GULP1 and SLC25A21 are categorized according to their genetic susceptibility to T2DM.The miR-548ab inhibitor shows beneficial effects in obese and diabetic mice.
