Models of lipid droplets growth and fission in adipocyte cells
Models of lipid droplets growth and fission in adipocyte cells
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DOI：
10.1016/j.yexcr.2015.06.001
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发表时间：
2015-08-15
影响因子：
3.7
通讯作者：
Sbarbati, Andrea
中科院分区：
文献类型：
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作者：
Boschi, Federico;Rizzatti, Vanni;Sbarbati, Andrea
脂滴（LD）是专门用于储存脂质的球形细胞内含物。众所周知，脂质的过度积累导致几种人类世界性疾病，如肥胖症、2型糖尿病、肝脂肪变性和动脉粥样硬化。脂肪细胞中LDs的大小从几分之一微米到几百微米不等，且与脂肪含量有关，但其生长仍是一个令人困惑的问题。有人认为，LD的大小可以增长，由于融合过程中，通过合并两个较小的LD获得一个更大的LD，但这些事件似乎是罕见的，难以观察到。许多其他过程被认为涉及LD的数量和生长，如从头形成和通过预先存在的液滴中的额外中性脂质沉积的生长。此外，LD的数量和大小受催化剂和吸收或与其他细胞器的相互作用的影响。这些过程的理解可能有助于限制与脂质积累有关的病理学。在这项研究中，考虑了LD的大小分布、数量和未成熟（n =12）、成熟（n=12，分化10天）和脂解（n=12）3 T3-L1脂肪细胞的总体积。油红O染色后，在36个细胞中测量到超过11，000个LD。在以前的工作中，蒙特卡罗模拟被用来模拟LD之间的融合过程。我们发现，考虑到融合是作用于LD的唯一过程，成熟脂肪细胞的尺寸分布可以从提供非常高的融合事件率的未成熟细胞的尺寸分布开始通过数值模拟获得。在本文中，蒙特卡罗模拟开发，以模拟激光二极管之间的相互作用，考虑到许多其他过程，除了融合（新星形成和通过预先存在的液滴中的额外中性脂质沉积的生长），以便再现LD生长，并且我们还模拟了催化剂（分裂和通过中性脂质从预先存在的液滴中排出的减少）以再现在脂解条件下观察到的它们的尺寸减小。结果表明，每个单独的过程，单独考虑，不能被认为是唯一负责观察到的大小变化，但其中不止一个，一起玩，可以很好地再现实验数据。(C)由Elsevier Inc.出版。
Lipid droplets (LD) are spherical cellular inclusion devoted to lipids storage. It is well known that excessive accumulation of lipids leads to several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis and atherosclerosis. LDs' size range from fraction to one hundred of micrometers in adipocytes and is related to the lipid content, but their growth is still a puzzling question. It has been suggested that LDs can grow in size due to the fusion process by which a larger LD is obtained by the merging of two smaller LDs, but these events seems to be rare and difficult to be observed. Many other processes are thought to be involved in the number and growth of LDs, like the de novo formation and the growth through additional neutral lipid deposition in pre-existing droplets. Moreover the number and size of LDs are influenced by the catabolism and the absorption or interaction with other organelles. The comprehension of these processes could help in the confinement of the pathologies related to lipid accumulation. In this study the LDs' size distribution, number and the total volume of immature (n=12), mature (n=12, 10-days differentiated) and lipolytic (n=12) 3T3-L1 adipocytes were considered. More than 11,000 LDs were measured in the 36 cells after Oil Red O staining. In a previous work Monte Carlo simulations were used to mimic the fusion process alone between LDs. We found that, considering the fusion as the only process acting on the LDs, the size distribution in mature adipocytes can be obtained with numerical simulation starting from the size distribution in immature cells provided a very high rate of fusion events. In this paper Monte Carlo simulations were developed to mimic the interaction between LDs taking into account many other processes in addition to fusion (de nova formation and the growth through additional neutral lipid deposition in pre-existing droplets) in order to reproduce the LDs growth and we also simulated the catabolism (fission and the decrease through neutral lipid exit from pre-existing droplets) to reproduce their size reduction observed in lipolytic conditions. The results suggest that each single process, considered alone, can not be considered the only responsible for the size variation observed, but more than one of them, playing together, can quite well reproduce the experimental data. (C) 2015 Published by Elsevier Inc.