SIRT6对小鼠米色脂肪细胞适应性产热功能的影响  

Effect of SIRT6 on adaptive thermogenesis in mouse beige fat cells

作　　者：韩在祺 崔佰吉[1] 冯波[1] 姚璐 HAN Zai-qi;CUI Bai-ji;FENG Bo;YAO Lu(Jilin Medical University,Jilin 132013,China)

机构地区：[1]吉林医药学院,吉林吉林132013

出　　处：《中国病理生理杂志》2018年第10期1827-1833,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81803221);吉林省教育厅项目(No.JJKH20180824KJ);吉林省中医药科技项目(No.2018123);吉林市科技创新发展计划项目(No.201831717)

摘　　要：目的:探索沉默信息调节因子6(SIRT6)对小鼠米色脂肪细胞适应性产热功能的影响及其机制。方法:利用Seahorse能量代谢分析仪和real-time PCR检测SIRT6对小鼠原代米色脂肪细胞线粒体呼吸的调控作用及产热基因表达的情况;在HEK293A细胞和小鼠原代米色脂肪细胞中利用免疫共沉淀(Co-IP)实验检测SIRT6和过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)的相互作用;利用免疫沉淀(IP)实验检测SIRT6对PGC-1α乙酰化水平的影响,并通过双萤光素酶报告基因实验检测SIRT6对PGC-1α转录辅激活活性的调控作用。结果:过表达SIRT6可增加小鼠原代米色脂肪细胞的氧气消耗速率,上调产热基因的表达,Co-IP实验说明SIRT6与PGC-1α存在相互作用,IP实验表明SIRT6会去乙酰化PGC-1α,双萤光素酶报告基因实验证实SIRT6会协同增强PGC-1α的转录辅激活活性。结论:SIRT6通过去乙酰化PGC-1α增强小鼠原代米色脂肪细胞的适应性产热,从而促进能量消耗。AIM:To study the effect of silent information regulator 6(SIRT6)on adaptive thermogenesis and its mechanism in the beige fat cells.METHODS:SIRT6 over-expression in mouse primary beige fat cells was induced by Ad-virus system.Seahorse XF instrument and real-time PCR were used to analyze the function of SIRT6 on mitochondrial respiration and the thermogenic gene expression.The interaction and regulation of SIRT6 on peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α)acetylation were examined by the methods of co-immunoprecipitation(Co-IP)and immunoprecipitation(IP)in both HEK293A cells and mouse primary beige fat cells.The dual-luciferase reporter assay was used to testify the effect of SIRT6 on the activity of transcriptional coactivator PGC-1α.RESULTS:The oxygen consumption rates and the expression of thermogenic genes were upregulated in mouse primary beige fat cells after infecting with Ad-Flag-Sirt6.The results of Co-IP showed an interaction between SIRT6 and PGC-1α,and the results of IP suggested that SIRT6 deacetylated PGC-1α.The results of dual-luciferase reporter assay proved that SIRT6 activated the transcriptional coactivator PGC-1α.CONCLUSION:SIRT6 stimulates adaptive thermogenesis and increases energy expenditure through deacetylation of PGC-1αin mouse primary beige fat cells.

关 键 词：沉默信息调节因子6 米色脂肪细胞 能量代谢 适应性产热 过氧化物酶体增殖物激活受体γ辅激活因子1α 

分 类 号：R589.2[医药卫生—内分泌] R363.2[医药卫生—内科学]