Regulation of adipose triglyceride lipase by rosiglitazone.
Regulation of adipose triglyceride lipase by rosiglitazone.
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DOI：
10.1111/j.1463-1326.2008.00916.x
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Belury MA
中科院分区：
文献类型：
--
作者：
Liu LF;Purushotham A;Wendel AA;Koba K;DeIuliis J;Lee K;Belury MA
目的：阐明罗格列酮调节脂肪甘油三酯脂肪酶(ATGL)的机制。雄性C57BL/6小鼠每天灌胃罗格列酮(10 mg/kg体重)，称量脂肪组织并保存，进行ATGL的mRNA和蛋白质分析。同时，用insulin/dexamethasone/3-isobutyl-1-methlxanthine鸡尾酒或罗格列酮诱导前脂肪细胞(3T3-L1)分化，用实时荧光定量聚合酶链式反应、免疫印迹和免疫组织化学方法检测其表达水平。罗格列酮同时促进前脂肪细胞向功能性脂肪细胞分化，并诱导ATGL的mRNA水平。过氧化物酶体增殖物激活受体-γ(PPARγ)拮抗剂双酚A二缩水甘油醚显著抑制罗格列酮诱导分化的3T3-L1脂肪细胞ATG1mRNA的表达，但不影响其蛋白水平。在肾上腺素存在的情况下，罗格列酮刺激游离脂肪酸的释放和二甘油酰基转移酶-1(DGAT-1)的表达增加，提示ATGL和DGAT-1可能协同参与罗格列酮刺激的3T3-L1脂肪细胞的甘油三酯水解和脂肪酸再酯化。用罗格列酮或胰岛素处理3T3-L1脂肪细胞似乎不改变脂滴周围ATGL染色的定位。最后，我们发现，在蛋白质合成抑制剂放线菌酮存在的情况下，罗格列酮增加了3T3-L1脂肪细胞ATGL的mRNA水平，这表明罗格列酮对ATGL的调控是在转录水平上进行的。罗格列酮可能通过PPARγ介导的机制直接调节ATGL的转录。
To elucidate the mechanism by which rosiglitazone regulates adipose triglyceride lipase (ATGL). Male C57Bl/6 mice were treated with rosiglitazone daily (10 mg/kg body weight), and adipose tissues were weighed and preserved for mRNA and protein analysis of ATGL. In parallel, preadipocyte (3T3-L1) cells were differentiated with insulin/dexamethasone/3-isobutyl-1-methlxanthine cocktail or rosiglitazone, and ATGL levels were measured with real-time PCR, western blotting and immunohistochemistry. Rosiglitazone concomitantly promoted differentiation of pre-adipocytes to functional adipocytes and induced mRNA levels of ATGL. The peroxisome proliferator-activated receptor-γ (PPARγ) antagonist bisphenol A diglycidyl ether significantly abrogated the induction of mRNA, but not protein levels of ATGL by rosiglitazone in differentiated 3T3-L1 adipocytes. In the presence of epinephrine rosiglitazone stimulated free fatty acid release and increased diacylglycerol acyltransferase-1 (DGAT-1) mRNA suggest that ATGL and DGAT-1 may be cooperatively involved in rosiglitazone-stimulated triglyceride hydrolysis and fatty acid re-esterification in 3T3-L1 adipocytes. Treatment of 3T3-L1 adipocytes with rosiglitazone or insulin did not appear to alter localization of ATGL staining surrounding lipid droplets. Finally, we found that rosiglitazone increased ATGL mRNA levels in 3T3-L1 adipocytes in the presence of cycloheximide, an inhibitor of protein synthesis, suggesting that rosiglitazone regulation of ATGL occurs at the transcriptional level. Rosiglitazone directly regulates transcription of ATGL, likely through a PPARγ-mediated mechanism.
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