Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes
Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes
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DOI：
10.1152/ajpendo.00187.2006
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发表时间：
2006-11-01
影响因子：
5.1
通讯作者：
Owens, Randall J.
中科院分区：
文献类型：
--
作者：
Bodles, Angela M.;Banga, Anannya;Owens, Randall J.
脂联素是一种脂肪细胞来源的血清蛋白，在能量平衡、肥胖和胰岛素敏感性中起重要作用。使用蔗糖梯度和蛋白质印迹的非变性凝胶，我们研究了脂联素亚型分泌的人脂肪组织，人和小鼠脂肪细胞，和细胞系在体外加入吡格列酮。体外脂肪组织分泌的主要形式是高分子量（HMW）亚型，存在少量低分子量（LMW）形式。体外添加吡格列酮（1-3 μ M）可增加HMW亚型的分泌，对其他亚型无显著影响。还检查了吡格列酮给药后人脂肪组织脂联素mRNA水平的变化。未检测到差异，表明吡格列酮的作用不是在转录水平，而是在分泌途径的转录后阶段。进行额外的实验以确定脂联素表达在其他脂肪细胞中是否在机制上相似。原代人脂肪细胞检查显示，吡格列酮处理后细胞内HMW亚型增加，LMW形式减少，分泌型HMW形式相应增加。在原代小鼠脂肪细胞、3 T3-F422 A细胞和SGBS人脂肪细胞中观察到相似的结果，尽管细胞类型之间HMW和LMW亚型的分布存在明显差异。尽管种属之间的亚型存在差异，但在所有情况下，吡格列酮均可增加脂联素HMW形式的分泌。
Adiponectin is an adipocyte-derived serum protein that plays important roles in energy homeostasis, obesity, and insulin sensitivity. Using sucrose gradients and Western blotting of nondenaturing gels, we examined the adiponectin isoforms secreted from human adipose tissue, human and mouse adipocytes, and cell lines in response to pioglitazone added in vitro. The predominant form secreted from adipose tissue in vitro was the high-molecular-weight (HMW) isoform, with small amounts of low-molecular-weight (LMW) forms present. The addition of pioglitazone (1-3 mu M) in vitro increased the secretion of the HMW isoform, with no significant effect on the other isoforms. Human adipose tissue was also examined for changes in adiponectin mRNA levels upon pioglitazone treatment. No difference was detected, suggesting that the effect of pioglitazone is not at the transcriptional level but, rather, at a posttranscriptional phase of the secretory pathway. Additional experiments were conducted to determine whether adiponectin expression was mechanistically similar in other adipose cells. Examination of primary human adipocytes revealed an increase in intracellular HMW isoform with a decline in LMW forms following pioglitazone treatment, with a corresponding increase in the secreted HMW form. Similar results were observed with primary mouse adipocytes, 3T3-F422A cells, and SGBS human adipocyte cells, although differences in the distribution of HMW and LMW isoforms were apparent between cell types. Although there are differences in isoforms between species, in all cases pioglitazone served to increase the secretion of the HMW form of adiponectin.