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Title: Models of lipid droplets growth and fission in adipocyte cells

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 11,000more » 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 novo 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. - Highlights: The growth and fission of the lipid droplets (LDs) were computationally simulated. To write and test the growth and fission models more than 110,000 LDs were measured. The usual processes considered alone, are not able to justify the experimental data. Some processes, playing together, can explain the growth and fission.« less
Authors:
 [1] ; ;  [2] ;  [3]
  1. Department of Computer Science, University of Verona, Strada Le Grazie 15, 37134 Verona (Italy)
  2. Department of Medicine, Geriatric Section, University of Verona, Piazzale Stefani 1, 37126 Verona (Italy)
  3. Department of Neurological and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona (Italy)
Publication Date:
OSTI Identifier:
22462319
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 336; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARTERIOSCLEROSIS; CATABOLISM; CELL CONSTITUENTS; COMPUTERIZED SIMULATION; DROPLETS; EXPERIMENTAL DATA; FATS; FISSION; LIVER; METABOLIC DISEASES; MONTE CARLO METHOD; NITROGEN 12; PATHOLOGY; TRIGLYCERIDES