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YAP1 调节 PPARG 和 RXR alpha 的表达,影响绵羊前体脂肪细胞的增殖和分化。

YAP1 regulates PPARG and RXR alpha expression to affect the proliferation and differentiation of ovine preadipocyte.

机构信息

Institute of Sheep and Goat Science, Nanjing Agricultural University, Nanjing, China.

Portal Agri-Industries Co, Ltd, Nanjing, China.

出版信息

J Cell Biochem. 2019 Dec;120(12):19578-19589. doi: 10.1002/jcb.29265. Epub 2019 Jul 11.

Abstract

Adipose tissue development is regulated by a serial of developmental signaling pathways. The Hippo pathway is a novel signaling cascade closely associated with adipogenesis. While most of Hippo pathway components had been verified that have a vital role in preadipocytes proliferation and differentiation, little is known about the function of Yes-associated protein 1 (YAP1) in mammalian adipose tissue development. Therefore, we investigated the role of YAP1 in ovine adipose tissue development by in vitro and in vivo experiments. We observed that the adipocyte size in subcutaneous adipose tissue increased with development. YAP1 expression increased during adipose tissue development, while decreased during the differentiation of ovine preadipocytes in vitro. YAP1 knockdown notably promoted lipid accumulation and suppressed ovine preadipocyte proliferation. In addition, we observed that YAP1 deficiency significantly upregulated peroxisome proliferator-activated receptor gamma (PPARG) and retinoid X receptor alpha (RXR alpha) expression. By contrast, overexpression of YAP1 led to the suppression of preadipocyte differentiation, lipid droplets formation, and PPARG expression. In brief, our findings demonstrated that YAP1 regulates the proliferation and differentiation of ovine preadipocyte via altering PPARG and RXR alpha expression.

摘要

脂肪组织的发育受一系列发育信号通路的调节。Hippo 通路是一种与脂肪生成密切相关的新型信号级联。虽然 Hippo 通路的大多数成分已被证实对前体脂肪细胞的增殖和分化具有重要作用,但对于哺乳动物脂肪组织发育中 Yes 相关蛋白 1(YAP1)的功能知之甚少。因此,我们通过体外和体内实验研究了 YAP1 在绵羊脂肪组织发育中的作用。我们观察到皮下脂肪组织中的脂肪细胞大小随着发育而增加。YAP1 的表达在脂肪组织发育过程中增加,而在体外绵羊前体脂肪细胞的分化过程中减少。YAP1 敲低显著促进了脂质积累,并抑制了绵羊前体脂肪细胞的增殖。此外,我们观察到 YAP1 缺失显著上调过氧化物酶体增殖物激活受体γ(PPARG)和视黄醇 X 受体α(RXRα)的表达。相比之下,YAP1 的过表达导致前体脂肪细胞分化、脂滴形成和 PPARG 表达受到抑制。总之,我们的研究结果表明,YAP1 通过改变 PPARG 和 RXRα 的表达来调节绵羊前体脂肪细胞的增殖和分化。

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