Adiponectin gene activation by thiazolidinediones requires PPAR gamma 2, but not C/EBP alpha-evidence for differential regulation of the aP2 and adiponectin genes.
Adiponectin gene activation by thiazolidinediones requires PPAR gamma 2, but not C/EBP alpha-evidence for differential regulation of the aP2 and adiponectin genes.
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噻唑烷二酮类化合物激活脂联素基因需要 PPAR gamma 2，但不需要 C/EBP α 证据来对 aP2 和脂联素基因进行差异调节。
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
U. Smith
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作者：
B. Gustafson;Maia M. Jack;S. Cushman;U. Smith
我们通过稳定表达PPARgamma 2或C/EBP alpha，检测了PPARgamma 2和C/EBP alpha对脂联素和aP 2基因激活的作用。在表达C/EBP α的细胞中，在向脂肪细胞分化的过程中，PPAR γ 2而不是PPAR γ 1的mRNA显著增加。两种感染的细胞系均分化为脂肪细胞表型，并且aP 2和脂联素的mRNA平行增加。然而，当C/EBP α存在时，脂联素mRNA显著升高，表明该转录因子对完整基因激活很重要。噻唑烷二酮类药物在C/EBP α缺乏的情况下显著激活了表达PPAR γ 2的细胞中的基因，这表明脂联素启动子可能具有功能性的PPAR γ反应元件。几个观察结果表明脂联素和aP 2基因在脂肪细胞中可以被不同地调节：（1）托吡酯，一种具有减肥特性的抗癫痫药，增加脂联素mRNA水平和分泌，但不像噻唑烷二酮类药物那样增加aP 2表达：（2）IL-6减少脂联素，但显著增加aP 2表达;（3）TNF α抑制脂联素，但矛盾的是增加了C/EBP α缺失细胞中PPAR γ 2感染的aP 2表达。这些数据表明，脂联素基因的激活可以从对成脂基因的影响中分离出来。
We examined the role of PPAR gamma 2 and C/EBP alpha for adiponectin and aP2 gene activation in C/EBP alpha(-/-) fibroblasts by stably expressing PPAR gamma 2 or C/EBP alpha. PPAR gamma 2, but not PPAR gamma 1, mRNA markedly increased during the differentiation to adipocytes in cells expressing C/EBP alpha. Both infected cell lines differentiated to an adipocyte phenotype and the mRNA for both aP2 and adiponectin increased in parallel. However, adiponectin mRNA was considerably higher when C/EBP alpha was present, suggesting that this transcription factor is important for full gene activation. Thiazolidinediones markedly activated the gene in PPAR gamma 2-expressing cells in the absence of C/EBP alpha, suggesting that the adiponectin promoter may have functional PPAR gamma-response elements. Several observations showed that the adiponectin and aP2 genes can be differentially regulated in adipocytes: (1) Topiramate, an anti-epileptic agent with weight-reducing properties, increased adiponectin mRNA levels and secretion, but did not, like the thiazolidinediones, increase aP2 expression; (2) IL-6 reduced adiponectin, but significantly increased, aP2 expression; and (3) TNFalpha inhibited adiponectin, but paradoxically increased, aP2 expression in PPAR gamma 2-infected C/EBP alpha null cells. These data show that activation of the adiponectin gene can be separated from effects on adipogenic genes.