The origin and physiological significance of lipid droplets (LDs) in the nucleus is not clear. Here we show that nuclear LDs in hepatocytes are derived from apolipoprotein B (ApoB)-free lumenal LDs, a precursor to very low-density lipoproprotein (VLDL) generated in the ER lumen by microsomal triglyceride transfer protein. ApoB-free lumenal LDs accumulate under ER stress, grow within the lumen of the type I nucleoplasmic reticulum, and turn into nucleoplasmic LDs by disintegration of the surrounding inner nuclear membrane. Oleic acid with or without tunicamycin significantly increases the formation of nucleoplasmic LDs, to which CDP-choline diacylglycerol phosphotransferase α (CCTα) is recruited, resulting in activation of phosphatidylcholine (PC) synthesis. Perilipin-3 competes with CCTα in binding to nucleoplasmic LDs, and thus, knockdown and overexpression of perilipin-3 increases and decreases PC synthesis, respectively. The results indicate that nucleoplasmic LDs in hepatocytes constitute a feedback mechanism to regulate PC synthesis in accordance with ER stress.

脂质滴（LDs）在细胞核中的起源和生理意义尚不清楚。在这里，我们显示肝细胞中的核LDs来自无载脂蛋白B（ApoB）的管腔LDs，ER内腔中通过微粒体甘油三酸酯转移蛋白产生的极低密度脂蛋白（VLDL）的前体。不含ApoB的管腔LD在内质网应激下积累，在I型核质网腔内生长，并通过周围内核膜的分解而变成核质LD。具有或不具有衣霉素的油酸显着增加了核质LD的形成，向其募集了CDP-胆碱二酰基甘油磷酸转移酶α（CCTα），从而激活了磷脂酰胆碱（PC）的合成。Perilipin-3与CCTα竞争结合核质LD，因此，Perilipin-3的敲低和过表达分别增加和减少PC合成。结果表明，肝细胞中的核质LDs构成了根据ER应激调节PC合成的反馈机制。