HMGA1 overexpression in adipose tissue impairs adipogenesis and prevents diet-induced obesity and insulin resistance.
HMGA1 overexpression in adipose tissue impairs adipogenesis and prevents diet-induced obesity and insulin resistance.
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DOI：
10.1038/srep14487
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发表时间：
2015-09-28
影响因子：
4.6
通讯作者：
Riu E
中科院分区：
文献类型：
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作者：
Arce-Cerezo A;García M;Rodríguez-Nuevo A;Crosa-Bonell M;Enguix N;Peró A;Muñoz S;Roca C;Ramos D;Franckhauser S;Elias I;Ferre T;Pujol A;Ruberte J;Villena JA;Bosch F;Riu E
高迁移率族A1（HMGA1）蛋白是在胚胎发生、肿瘤发生和免疫应答过程中调节染色质结构和基因表达的非组蛋白。体外研究表明，HMGA1蛋白可能需要调节脂肪形成。为了研究HMGA1在体内的作用，我们产生了在脂肪组织中过表达HMGA1的转基因小鼠。HMGA 1转基因小鼠显示白色和棕色脂肪组织质量显著减少，这与参与脂肪形成的基因下调和伴随的前脂肪细胞标志物上调有关。脂肪生成减少和脂肪量减少与葡萄糖稳态改变无关，因为喂食常规饲料的HMGA1转基因小鼠显示出正常的葡萄糖耐量和胰岛素敏感性。然而，当喂食高脂饮食时，HMGA1的过度表达导致体重增加减少，脂肪量减少，但改善胰岛素敏感性和葡萄糖耐量。虽然HMGA1转基因小鼠由于脂肪形成受损而表现出脂肪组织中葡萄糖摄取受损，但在骨骼肌中观察到的葡萄糖摄取增加可能是葡萄糖稳态改善的原因。我们的研究结果表明，HMGA 1在体内白色和棕色脂肪形成的调节中起着重要的作用，并表明脂肪细胞分化受损和脂肪量减少并不总是与全身葡萄糖稳态受损相关。
High-Mobility-Group-A1 (HMGA1) proteins are non-histone proteins that regulate chromatin structure and gene expression during embryogenesis, tumourigenesis and immune responses. In vitro studies suggest that HMGA1 proteins may be required to regulate adipogenesis. To examine the role of HMGA1 in vivo, we generated transgenic mice overexpressing HMGA1 in adipose tissues. HMGA1 transgenic mice showed a marked reduction in white and brown adipose tissue mass that was associated with downregulation of genes involved in adipogenesis and concomitant upregulation of preadipocyte markers. Reduced adipogenesis and decreased fat mass were not associated with altered glucose homeostasis since HMGA1 transgenic mice fed a regular-chow diet exhibited normal glucose tolerance and insulin sensitivity. However, when fed a high-fat diet, overexpression of HMGA1 resulted in decreased body-weight gain, reduced fat mass, but improved insulin sensitivity and glucose tolerance. Although HMGA1 transgenic mice exhibited impaired glucose uptake in adipose tissue due to impaired adipogenesis, the increased glucose uptake observed in skeletal muscle may account for the improved glucose homeostasis. Our results indicate that HMGA1 plays an important function in the regulation of white and brown adipogenesis in vivo and suggests that impaired adipocyte differentiation and decreased fat mass is not always associated with impaired whole-body glucose homeostasis.