MIG12 is involved in the LXR activation-mediated induction of the polymerization of mammalian acetyl-CoA carboxylase
MIG12 is involved in the LXR activation-mediated induction of the polymerization of mammalian acetyl-CoA carboxylase
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MIG12 参与 LXR 激活介导的哺乳动物乙酰辅酶 A 羧化酶聚合诱导
DOI：
10.1016/j.bbrc.2021.06.040
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发表时间：
2021
影响因子：
3.1
通讯作者：
Inoue Jun
中科院分区：
文献类型：
--
作者：
Izumi Akiko;Hiraguchi Haruka;Kodaka Manami;Ikeuchi Emina;Narita Junko;Kobayashi Rina;Matsumoto Yu;Suzuki Tsukasa;Yamamoto Yuji;Sato Ryuichiro;Inoue Jun
肝脏X受体（Liver X receptor，LXR）α和β是一个核受体家族，通过调控脂肪酸合成相关基因的表达来调节脂肪生成，其中编码MIG12的MID1IP1是LXR的靶基因。MIG12通过刺激乙酰辅酶A羧化酶（ACC）的聚合介导的活化来诱导脂肪酸合成。在这里，我们发现LXR的激活通过增加MIG12的表达来刺激HepG2细胞中的ACC聚合。MID1IP1的敲低完全消除了刺激。MIG12的亮氨酸拉链结构域的突变降低了MIG12和ACC之间的相互作用，从而降低了MIG12刺激ACC聚合的能力。这些结果表明，LXR的激活不仅通过诱导编码脂肪生成酶的基因，而且通过MIG12刺激ACC聚合来刺激脂肪生成。
Liver X receptors (LXR) α and β are a family of nuclear receptors that regulate lipogenesis by controlling the expression of the genes involved in the synthesis of fatty acids.MID1IP1, which encodes MIG12, is a target gene of LXR. MIG12 induces fatty acid synthesis by stimulating the polymerization-mediated activation of acetyl-CoA carboxylase (ACC). Here, we show that LXR's activation stimulates ACC polymerization in HepG2 cells by increasing the expression of MIG12. A knockdown ofMID1IP1abrogated the stimulation completely. The mutations of MIG12's leucine-zipper domain reduced the interaction between MIG12 and ACC, thus decreasing the MIG12's capacity to stimulate ACC polymerization. These results indicate that LXR's activation stimulates lipogenesis not only through the induction of the genes encoding lipogenic enzymes but also through MIG12's stimulation of ACC polymerization.