Hepatocytes Deficient in Nuclear Envelope Protein Lamina-associated Polypeptide 1 are an Ideal Mammalian System to Study Intranuclear Lipid Droplets.
Hepatocytes Deficient in Nuclear Envelope Protein Lamina-associated Polypeptide 1 are an Ideal Mammalian System to Study Intranuclear Lipid Droplets.
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DOI：
10.1016/j.jlr.2022.100277
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发表时间：
2022-10
影响因子：
6.5
通讯作者：
Shin, Ji-Yeon
中科院分区：
文献类型：
--
作者：
Ostlund, Cecilia;Hernandez-Ono, Antonio;Turk, Samantha J.;Dauer, William T.;Ginsberg, Henry N.;Worman, Howard J.;Shin, Ji-Yeon
关键词：
脂滴（LD）通常被认为在ER中合成并在细胞质中利用。然而，在一些细胞的细胞核内观察到LD，尽管最近对核LD的研究集中在培养的细胞系上。为了更好地了解体内发生的核LD，在此我们检测了小鼠原代肝细胞中的LD，这些小鼠原代肝细胞在核膜蛋白层粘连蛋白相关多肽1（LAP 1）耗竭后。显微镜图像分析表明，LAP 1耗尽肝细胞含有频繁的核LD，这不同于其相关蛋白质的细胞质LD。我们发现1型核浆网，这是内核膜的内陷，往往与核LD在这些肝细胞。此外，从小鼠肝细胞的核被膜蛋白核纤层蛋白A和C的体内耗竭导致严重异常的核形态，但显着较少的核LD比在LAP 1耗竭后观察到的。此外，我们发现高脂饮食喂养和禁食的小鼠增加细胞质脂质在LAP 1耗尽的肝细胞，但减少核LD，表明LD形成与营养状态的关系。最后，微粒体甘油三酯转移蛋白的耗竭并没有改变LAP 1耗竭肝细胞中核LD的频率，这表明在这些细胞中核LD的生物发生并不需要它。总之，这些数据表明，LAP1耗竭肝细胞代表了一个理想的哺乳动物系统，以研究核LD的生物发生及其在细胞核和细胞质之间的分配，以响应体内营养状态和细胞代谢的变化。
Lipid droplets (LDs) are generally considered to be synthesized in the ER and utilized in the cytoplasm. However, LDs have been observed inside nuclei in some cells, although recent research on nuclear LDs has focused on cultured cell lines. To better understand nuclear LDs that occur in vivo, here we examined LDs in primary hepatocytes from mice following depletion of the nuclear envelope protein lamina-associated polypeptide 1 (LAP1). Microscopic image analysis showed that LAP1-depleted hepatocytes contain frequent nuclear LDs, which differ from cytoplasmic LDs in their associated proteins. We found type 1 nucleoplasmic reticula, which are invaginations of the inner nuclear membrane, are often associated with nuclear LDs in these hepatocytes. Furthermore, in vivo depletion of the nuclear envelope proteins lamin A and C from mouse hepatocytes led to severely abnormal nuclear morphology, but significantly fewer nuclear LDs than were observed upon depletion of LAP1. In addition, we show both high-fat diet feeding and fasting of mice increased cytoplasmic lipids in LAP1-depleted hepatocytes but reduced nuclear LDs, demonstrating a relationship of LD formation with nutritional state. Finally, depletion of microsomal triglyceride transfer protein did not change the frequency of nuclear LDs in LAP1-depleted hepatocytes, suggesting that it is not required for the biogenesis of nuclear LDs in these cells. Together, these data show that LAP1-depleted hepatocytes represent an ideal mammalian system to investigate the biogenesis of nuclear LDs and their partitioning between the nucleus and cytoplasm in response to changes in nutritional state and cellular metabolism in vivo.
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影响因子：
7.8
作者：
GERACE, L;BLUM, A;BLOBEL, G
通讯作者：
BLOBEL, G
影响因子：
5.6
作者：
Jin Y;Tan Y;Zhao P;Ren Z
通讯作者：
Ren Z
DOI：
10.1016/j.jcmgh.2017.06.005
发表时间：
2017-11
影响因子：
7.2
作者：
Kwan R;Brady GF;Brzozowski M;Weerasinghe SV;Martin H;Park MJ;Brunt MJ;Menon RK;Tong X;Yin L;Stewart CL;Omary MB
通讯作者：
Omary MB
影响因子：
6.5
作者：
Chitraju, Chandramohan;Troetzmueller, Martin;Spener, Friedrich
通讯作者：
Spener, Friedrich
影响因子：
4.8
作者：
MARTIN, L;CRIMAUDO, C;GERACE, L
通讯作者：
GERACE, L