为了研究阿勒泰大尾羊和小尾寒羊不同脂肪组织及其他组织之间基因表达的差异,探讨脂肪与肥胖相关基因(fat mass and obesity associated gene,FTO)与绵羊体脂沉积的相关性。随机各选择6只6月龄雄性阿勒泰大尾羊和小尾寒羊,禁食24h后屠宰...为了研究阿勒泰大尾羊和小尾寒羊不同脂肪组织及其他组织之间基因表达的差异,探讨脂肪与肥胖相关基因(fat mass and obesity associated gene,FTO)与绵羊体脂沉积的相关性。随机各选择6只6月龄雄性阿勒泰大尾羊和小尾寒羊,禁食24h后屠宰,分别采集下丘脑、海马、背最长肌、心肌和脂肪组织样本,应用冰冻组织切片技术,测定脂肪细胞的面积,用real-time PCR检测FTO基因在各组织中的表达水平。结果显示,阿勒泰大尾羊尾脂脂肪细胞面积极显著高于肾周脂脂肪细胞面积(P<0.01)。阿勒泰大尾羊与小尾寒羊下丘脑和海马FTO基因表达水平无显著差异,背最长肌、心肌FTO基因表达水平阿勒泰大尾羊的极显著高于小尾寒羊的(P<0.01),肾周脂中FTO基因表达水平阿勒泰大尾羊的显著高于小尾寒羊的(P<0.05)。阿勒泰大尾羊肾周脂、心周脂和尾脂中FTO基因表达水平在肾周脂、心周脂、尾脂之间无显著差异。结果表明,FTO基因表达水平在阿勒泰大尾羊和小尾寒羊之间存在品种间的差异。展开更多
Background Non-alcoholic fatty liver disease （NAFLD） is a complex disorder and has been closely linked to obesity.The fat mass and obesity-associated （FTO） gene is a newly discovered gene related to obesity,which ...Background Non-alcoholic fatty liver disease （NAFLD） is a complex disorder and has been closely linked to obesity.The fat mass and obesity-associated （FTO） gene is a newly discovered gene related to obesity,which enhances oxidative stress and tipogenesis in NAFLD.The forkhead transcription factor O1 （FoxO1） is another important gene involved in NAFLD,which causes lipid disorders when insulin resistance appears in the liver.However,the interactions between FTO and FoxO1 during the pathogenesis of NAFLD have not been fully elucidated.This study was designed to identify the relationship between these two factors that are involved in the development of NAFLD.Methods This study includes two parts referred to as animal and cell experiments.Twelve female SPF C57BL/6 mice were fed a high-fat diet to serve as an NAFLD animal model.Aspartate aminotransferase （AST）,alanine aminotransferase （ALT）,total triglyceride （TG）,total cholesterol （TC）,alkaline phosphatase （ALP）,high-density lipoprotein （HDL）,and low-density lipoprotein （LDL） were measured.Immunohistochemical analysis was used to detect the expression and histological localization of FTO,FoxO1,and adenosine monophosphate （AMP）-activated protein kinase （AMPK）.The L02 cells were exposed to high fat for 24,48,or 72 hours.Oil red O staining was used to detect intracellular lipid droplets.Reverse transcription-polymerase chain reaction was used for analyzing the levels of FTO and FoxO1 mRNA.Results At the end of 10 weeks,ALP,ALT,AST,and LDL were significantly increased （P ＜0.01）,while TC and TG were also significantly higher （P ＜0.05）.In addition,HDL was significantly decreased （P ＜0.05）.The FTO and FoxO1 proteins were weakly expressed in the control group,but both FTO and FoxO1 were expressed significantly higher （P ＜0.01） in the experimental group,and the expression of the two factors was significantly correlated.AMPK in the high-fat group showed a low level of correlation with FTO,but not with FoxO1展开更多
Background Genome-wide association studies for type 2 diabetes mellitus （T2DM） identified FTO gene as a locus conferring increased risk for common obesity in many populations with European ancestry. However, the inv...Background Genome-wide association studies for type 2 diabetes mellitus （T2DM） identified FTO gene as a locus conferring increased risk for common obesity in many populations with European ancestry. However, the involvement of FTO gene in obesity or T2DM related metabolic traits has not been consistently established in Chinese populations. The objective of this study was to investigate the association of FTO genetic polymorphisms with metabolic syndrome （MetS） in Han Chinese. Methods We tested 41 FTO single nucleotide polymorphisms （SNPs） for association between FTO and MetS-related traits. There were a total of 236 unrelated subjects （108 cases and 128 controls）, grouped according to the International Diabetes Federation （IDF） criteria. Results Of the 41 SNPs examined, only SNP rs8047395 exhibited statistical significance （P=-0.026） under a recessive model, after Bonferroni adjustment for multiple testing （OR 1.64, 95% CI 1.11-2.42; P=-0.014）. The common distributions of this polymorphism among Chineseawith a minor allele frequency （MAF） of 36% in the control group versus 48% in the Met$ group--greatly improved our test power in a relatively small sample size for an association study. Previously identified obesity- （or T2DM-） associated FTO SNPs were less common in Hart Chinese and were not associated with MetS in this study. No significant associations were found between our FTO SNPs and any endophenotypes of MetS. Conclusions A more common risk-conferring variant of FTO for MetS was identified in Han Chinese. Our study substantiated that genetic variations in FTO locus are involved in the pathogenesis of MetS.展开更多
FTO(fat mass and obesity associated)是肥胖症易感基因,表达于人体各组织,且在下丘脑中高表达。它能编码核酸去甲基化酶,通过去甲基化作用影响其他相关基因表达。FTO的基因多态性与体重指数(BMI)及肥胖症密切相关。FTO能够影响能量摄...FTO(fat mass and obesity associated)是肥胖症易感基因,表达于人体各组织,且在下丘脑中高表达。它能编码核酸去甲基化酶,通过去甲基化作用影响其他相关基因表达。FTO的基因多态性与体重指数(BMI)及肥胖症密切相关。FTO能够影响能量摄入及能量消耗,并通过多种途径诱导人群中肥胖症及2型糖尿病等相关疾病的发生,而FTO失活的小鼠能够避免肥胖发生。主要综述了FTO基因多态性与肥胖等疾病易感性的相关性、FTO可能的作用机制和FTO对人群中能量平衡的影响。展开更多
目的:探讨脂肪相关基因(fat mass and obesity associated gene,FTO)及其抑制剂大黄酸(rhein)在非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)中的作用。方法:采用高脂饲料喂养的方法构建NAFLD小鼠模型,利用灌胃的方式使...目的:探讨脂肪相关基因(fat mass and obesity associated gene,FTO)及其抑制剂大黄酸(rhein)在非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)中的作用。方法:采用高脂饲料喂养的方法构建NAFLD小鼠模型,利用灌胃的方式使用rhein进行治疗。为评估造模是否成功及药物治疗效果,分别采用H-E染色、油红染色确定小鼠肝细胞中脂肪沉积的情况,采用Western blot检测FTO蛋白在小鼠肝脏组织中的变化情况。结果:与普饲组相比,高脂组小鼠的摄食量明显降低(P<0.01),高脂+rhein组小鼠的体质量明显低于高脂组(P<0.05)。与高脂组相比,高脂+rhein组小鼠肝细胞中脂肪空泡明显减少,高脂组小鼠肝细胞中脂肪沉积明显多于普饲组,rhein灌胃的小鼠肝细胞中脂肪沉积明显减少。与高脂组相比,高脂+rhein组小鼠的脂肪代谢明显恢复。FTO蛋白在高脂组小鼠的肝组织中显著增多,而在高脂+rhein组小鼠肝组织中FTO蛋白的表达量明显回落。结论:Rhein可减少NAFLD小鼠模型中肝组织FTO蛋白的表达,有治疗NAFLD的潜能。展开更多
目的 研究体脂量和肥胖症相关基因（fat mass and obesity associated gene,FTO）单核苷酸多态性与新疆哈萨克族学龄儿童超重及肥胖症的关系.方法 应用聚合酶链反应-限制性片段长度多态性的方法,对141例超重及肥胖（病例组）的哈萨克族...目的 研究体脂量和肥胖症相关基因（fat mass and obesity associated gene,FTO）单核苷酸多态性与新疆哈萨克族学龄儿童超重及肥胖症的关系.方法 应用聚合酶链反应-限制性片段长度多态性的方法,对141例超重及肥胖（病例组）的哈萨克族学龄儿童和138名健康对照儿童FTO基因rs9939609位点进行分析,同时进行血糖、血脂、胰岛素测定.结果 FTO基因rs9939609在病例组和健康对照组中基因型频率分别为：AA型0.071和0.029,AT型0.511和0.428,TT型0.418和0.543,两组AA、AT和TT 3种基因型频率分布差异无统计学意义（χ^2=5.74,P=0.057）,但AA＋AT（突变纯合子＋突变杂合子）在病例组[0.582（82/141）]明显高于对照组[0.457（63/138）],差异具有统计学意义（χ^2=4.368,P=0.037）;且在两组人群中A等位基因频率差异具有统计学意义（χ^2=4.772,P=0.029）.病例组中AA＋AT基因型携带者的血糖水平[（4.88±0.51）mol/L]较TT基因型携带者[（4.68±0.56）mol/L]高,差异具有统计学意义.Logistic回归分析显示,A等位基因是超重及肥胖的独立危险因素（OR=0.527;95%CI：0.319～0.869）.结论 体脂量和肥胖症相关基因第1内含子rs9939609多态性和新疆哈萨克族学龄儿童超重及肥胖的发生具有相关性.展开更多
肥胖目前在世界范围内以极快的流行趋势和其带来的一系列相关疾病而引起全球的广泛重视。作为多因素复杂性状疾病,肥胖与遗传基因之间的相关性研究越来越深入。肥胖相关基因(fat mass and obesity associated gene,FTO)是首例被确认与...肥胖目前在世界范围内以极快的流行趋势和其带来的一系列相关疾病而引起全球的广泛重视。作为多因素复杂性状疾病,肥胖与遗传基因之间的相关性研究越来越深入。肥胖相关基因(fat mass and obesity associated gene,FTO)是首例被确认与肥胖密切相关基因,并在不同人群和动物中得到反复验证。目前针对FTO的研究越来越细致,从最初的遗传多态性研究向更深的表达调控机制及功能学研究拓展,本篇将对相关研究进展作一系统综述。展开更多
文摘为了研究阿勒泰大尾羊和小尾寒羊不同脂肪组织及其他组织之间基因表达的差异,探讨脂肪与肥胖相关基因(fat mass and obesity associated gene,FTO)与绵羊体脂沉积的相关性。随机各选择6只6月龄雄性阿勒泰大尾羊和小尾寒羊,禁食24h后屠宰,分别采集下丘脑、海马、背最长肌、心肌和脂肪组织样本,应用冰冻组织切片技术,测定脂肪细胞的面积,用real-time PCR检测FTO基因在各组织中的表达水平。结果显示,阿勒泰大尾羊尾脂脂肪细胞面积极显著高于肾周脂脂肪细胞面积(P<0.01)。阿勒泰大尾羊与小尾寒羊下丘脑和海马FTO基因表达水平无显著差异,背最长肌、心肌FTO基因表达水平阿勒泰大尾羊的极显著高于小尾寒羊的(P<0.01),肾周脂中FTO基因表达水平阿勒泰大尾羊的显著高于小尾寒羊的(P<0.05)。阿勒泰大尾羊肾周脂、心周脂和尾脂中FTO基因表达水平在肾周脂、心周脂、尾脂之间无显著差异。结果表明,FTO基因表达水平在阿勒泰大尾羊和小尾寒羊之间存在品种间的差异。
文摘Background Non-alcoholic fatty liver disease （NAFLD） is a complex disorder and has been closely linked to obesity.The fat mass and obesity-associated （FTO） gene is a newly discovered gene related to obesity,which enhances oxidative stress and tipogenesis in NAFLD.The forkhead transcription factor O1 （FoxO1） is another important gene involved in NAFLD,which causes lipid disorders when insulin resistance appears in the liver.However,the interactions between FTO and FoxO1 during the pathogenesis of NAFLD have not been fully elucidated.This study was designed to identify the relationship between these two factors that are involved in the development of NAFLD.Methods This study includes two parts referred to as animal and cell experiments.Twelve female SPF C57BL/6 mice were fed a high-fat diet to serve as an NAFLD animal model.Aspartate aminotransferase （AST）,alanine aminotransferase （ALT）,total triglyceride （TG）,total cholesterol （TC）,alkaline phosphatase （ALP）,high-density lipoprotein （HDL）,and low-density lipoprotein （LDL） were measured.Immunohistochemical analysis was used to detect the expression and histological localization of FTO,FoxO1,and adenosine monophosphate （AMP）-activated protein kinase （AMPK）.The L02 cells were exposed to high fat for 24,48,or 72 hours.Oil red O staining was used to detect intracellular lipid droplets.Reverse transcription-polymerase chain reaction was used for analyzing the levels of FTO and FoxO1 mRNA.Results At the end of 10 weeks,ALP,ALT,AST,and LDL were significantly increased （P ＜0.01）,while TC and TG were also significantly higher （P ＜0.05）.In addition,HDL was significantly decreased （P ＜0.05）.The FTO and FoxO1 proteins were weakly expressed in the control group,but both FTO and FoxO1 were expressed significantly higher （P ＜0.01） in the experimental group,and the expression of the two factors was significantly correlated.AMPK in the high-fat group showed a low level of correlation with FTO,but not with FoxO1
基金This study was supported by a grant from Beijing Natural Science Foundation （No. 7092085, PI： XIAO Xin-hua）.
文摘Background Genome-wide association studies for type 2 diabetes mellitus （T2DM） identified FTO gene as a locus conferring increased risk for common obesity in many populations with European ancestry. However, the involvement of FTO gene in obesity or T2DM related metabolic traits has not been consistently established in Chinese populations. The objective of this study was to investigate the association of FTO genetic polymorphisms with metabolic syndrome （MetS） in Han Chinese. Methods We tested 41 FTO single nucleotide polymorphisms （SNPs） for association between FTO and MetS-related traits. There were a total of 236 unrelated subjects （108 cases and 128 controls）, grouped according to the International Diabetes Federation （IDF） criteria. Results Of the 41 SNPs examined, only SNP rs8047395 exhibited statistical significance （P=-0.026） under a recessive model, after Bonferroni adjustment for multiple testing （OR 1.64, 95% CI 1.11-2.42; P=-0.014）. The common distributions of this polymorphism among Chineseawith a minor allele frequency （MAF） of 36% in the control group versus 48% in the Met$ group--greatly improved our test power in a relatively small sample size for an association study. Previously identified obesity- （or T2DM-） associated FTO SNPs were less common in Hart Chinese and were not associated with MetS in this study. No significant associations were found between our FTO SNPs and any endophenotypes of MetS. Conclusions A more common risk-conferring variant of FTO for MetS was identified in Han Chinese. Our study substantiated that genetic variations in FTO locus are involved in the pathogenesis of MetS.
文摘FTO(fat mass and obesity associated)是肥胖症易感基因,表达于人体各组织,且在下丘脑中高表达。它能编码核酸去甲基化酶,通过去甲基化作用影响其他相关基因表达。FTO的基因多态性与体重指数(BMI)及肥胖症密切相关。FTO能够影响能量摄入及能量消耗,并通过多种途径诱导人群中肥胖症及2型糖尿病等相关疾病的发生,而FTO失活的小鼠能够避免肥胖发生。主要综述了FTO基因多态性与肥胖等疾病易感性的相关性、FTO可能的作用机制和FTO对人群中能量平衡的影响。
文摘目的:探讨脂肪相关基因(fat mass and obesity associated gene,FTO)及其抑制剂大黄酸(rhein)在非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)中的作用。方法:采用高脂饲料喂养的方法构建NAFLD小鼠模型,利用灌胃的方式使用rhein进行治疗。为评估造模是否成功及药物治疗效果,分别采用H-E染色、油红染色确定小鼠肝细胞中脂肪沉积的情况,采用Western blot检测FTO蛋白在小鼠肝脏组织中的变化情况。结果:与普饲组相比,高脂组小鼠的摄食量明显降低(P<0.01),高脂+rhein组小鼠的体质量明显低于高脂组(P<0.05)。与高脂组相比,高脂+rhein组小鼠肝细胞中脂肪空泡明显减少,高脂组小鼠肝细胞中脂肪沉积明显多于普饲组,rhein灌胃的小鼠肝细胞中脂肪沉积明显减少。与高脂组相比,高脂+rhein组小鼠的脂肪代谢明显恢复。FTO蛋白在高脂组小鼠的肝组织中显著增多,而在高脂+rhein组小鼠肝组织中FTO蛋白的表达量明显回落。结论:Rhein可减少NAFLD小鼠模型中肝组织FTO蛋白的表达,有治疗NAFLD的潜能。
文摘肥胖目前在世界范围内以极快的流行趋势和其带来的一系列相关疾病而引起全球的广泛重视。作为多因素复杂性状疾病,肥胖与遗传基因之间的相关性研究越来越深入。肥胖相关基因(fat mass and obesity associated gene,FTO)是首例被确认与肥胖密切相关基因,并在不同人群和动物中得到反复验证。目前针对FTO的研究越来越细致,从最初的遗传多态性研究向更深的表达调控机制及功能学研究拓展,本篇将对相关研究进展作一系统综述。
