组成性激活的 Stat5A 和 Stat5B 促进脂肪生成。
Constitutively active Stat5A and Stat5B promote adipogenesis.
机构信息
Department of Environmental Biology, School of Medicine, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, 060-8638, Japan.
出版信息
Environ Health Prev Med. 2011 Jul;16(4):247-52. doi: 10.1007/s12199-010-0193-7. Epub 2010 Dec 1.
OBJECTIVE
The metabolic syndrome is an important social problem affecting many people in developed countries. Obesity is a leading cause of this syndrome, hence understanding molecular mechanisms underlying obesity is of prime importance for preventive medicine to develop novel methods to alleviate the corresponding social cost as well as for pharmaceutical companies to develop antimetabolic drugs.
METHODS
Since adipocytes play an important role in obesity, we explored the signaling pathways leading to differentiation of adipocytes. We used a preadipocyte cell line to monitor the differentiation of adipocytes, and virus-mediated gene transfer to assess the role of the transcription factor Stat5 in adipogenesis. Adipocyte differentiation was assessed by Northern blot and Western blot analyses as well as accumulation of fat droplets in cells. Promoter activity of the proadipogenic transcription factor peroxisome proliferator-activated receptor-gamma (PPARγ) was evaluated by luciferase assay.
RESULTS
Virus-mediated gene transfer of the constitutively active form of both Stat5A and Stat5B resulted in enhanced adipocyte differentiation in the absence of fetal bovine serum (FBS) as judged by expression of proadipogenic factors as well as accumulation of fat droplets in cells. Such a proadipogenic effect of Stat5 is, in part, mediated by its ability to enhance transcription of PPARγ, a master transcriptional regulator in adipogenesis.
CONCLUSION
The constitutively active form of Stat5A and Stat5B promoted adipocyte differentiation in the absence of FBS via induction of PPARγ.
目的
代谢综合征是一个影响许多发达国家人群的重要社会问题。肥胖是该综合征的主要病因，因此，了解肥胖的分子机制对于预防医学开发新的方法来减轻相应的社会成本以及制药公司开发抗代谢药物至关重要。
方法
由于脂肪细胞在肥胖中起着重要作用，我们探索了导致脂肪细胞分化的信号通路。我们使用前体脂肪细胞系来监测脂肪细胞的分化，并通过病毒介导的基因转移来评估转录因子 Stat5 在脂肪生成中的作用。通过 Northern blot 和 Western blot 分析以及细胞内脂肪滴的积累来评估脂肪细胞的分化。通过荧光素酶测定评估前脂肪生成转录因子过氧化物酶体增殖物激活受体-γ (PPARγ) 的启动子活性。
结果
病毒介导的两种 Stat5A 和 Stat5B 的组成激活形式的基因转移导致在没有胎牛血清 (FBS) 的情况下增强了脂肪细胞分化，这可以通过前脂肪生成因子的表达以及细胞内脂肪滴的积累来判断。Stat5 的这种前脂肪生成作用部分是通过其增强脂肪生成主转录调节剂 PPARγ 的转录能力来介导的。
结论
组成激活形式的 Stat5A 和 Stat5B 通过诱导 PPARγ 在没有 FBS 的情况下促进脂肪细胞分化。
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