Progesterone receptor membrane associated component 1 enhances obesity progression in mice by facilitating lipid accumulation in adipocytes
Progesterone receptor membrane associated component 1 enhances obesity progression in mice by facilitating lipid accumulation in adipocytes
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DOI：
10.1038/s42003-020-01202-x
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发表时间：
2020-09-04
影响因子：
5.9
通讯作者：
Suematsu, Makoto
中科院分区：
文献类型：
--
作者：
Furuhata, Ryogo;Kabe, Yasuaki;Suematsu, Makoto
前列腺素受体膜相关成分1（PGRMC 1）在细胞膜上表现出血红素依赖性二聚化，并与EGF受体和细胞色素P450结合以调节肿瘤增殖和化疗耐药性。然而，其生理功能仍然未知。在此，我们证明了PGRMC 1是脂肪形成所必需的，并且其表达被胰岛素或噻唑烷（一种PPAR γ激动剂）显著增强。血液二聚化的PGRMC 1与低密度脂蛋白受体（VLDL-R和LDL-R）或GLUT 4相互作用，以调节其向质膜的易位，促进脂肪细胞中的脂质摄取和积累以及从头脂肪酸合成。这些事件被CO通过干扰PGRMC 1二聚化而取消。小鼠脂肪组织中的PGRMC 1表达在由高脂肪饮食诱导的肥胖期间增强。此外，小鼠脂肪组织特异性PGRMC 1敲除可显着抑制高脂饮食诱导的脂肪细胞肥大。我们的研究结果表明，PGRMC 1通过其在脂肪细胞中的脂质和碳水化合物的代谢调节在发展肥胖中起关键作用。Ryogo Furuhata，Yasuaki Kabe等人发现PGRMC 1是小鼠脂肪生成所需的，并且其表达通过胰岛素或PPAR γ激动剂增加。他们发现，敲除PGRMC 1可以通过调节脂质的摄取和积累来防止饮食诱导的肥胖。
Progesterone receptor membrane associated component 1 (PGRMC1) exhibits haem-dependent dimerization on cell membrane and binds to EGF receptor and cytochromes P450 to regulate cancer proliferation and chemoresistance. However, its physiological functions remain unknown. Herein, we demonstrate that PGRMC1 is required for adipogenesis, and its expression is significantly enhanced by insulin or thiazolidine, an agonist for PPAR gamma. The haem-dimerized PGRMC1 interacts with low-density lipoprotein receptors (VLDL-R and LDL-R) or GLUT4 to regulate their translocation to the plasma membrane, facilitating lipid uptake and accumulation, and de-novo fatty acid synthesis in adipocytes. These events are cancelled by CO through interfering with PGRMC1 dimerization. PGRMC1 expression in mouse adipose tissues is enhanced during obesity induced by a high fat diet. Furthermore, adipose tissue-specific PGRMC1 knockout in mice dramatically suppressed high-fat-diet induced adipocyte hypertrophy. Our results indicate a pivotal role of PGRMC1 in developing obesity through its metabolic regulation of lipids and carbohydrates in adipocytes. Ryogo Furuhata, Yasuaki Kabe et al. discover that PGRMC1 is required for adipogenesis in mice and its expression is increased by insulin or PPAR gamma agonists. They find that knocking out PGRMC1 protects against diet-induced obesity by regulating lipid uptake and accumulation.