Abstract
Neutral lipids—involved in many cellular processes—are stored as lipid droplets (LD), those mainly cytosolic (cLD) along with a small nuclear population (nLD). nLD could be involved in nuclear-lipid homeostasis serving as an endonuclear buffering system that would provide or incorporate lipids and proteins involved in signalling pathways as transcription factors and as enzymes of lipid metabolism and nuclear processes. Our aim was to determine if nLD constituted a dynamic domain. Oleic-acid (OA) added to rat hepatocytes or HepG2 cells in culture produced cellular-phenotypic LD modifications: increases in TAG, CE, C, and PL content and in cLD and nLD numbers and sizes. LD increments were reversed on exclusion of OA and were prevented by inhibition of acyl-CoA synthetase (with Triacsin C) and thus lipid biosynthesis. Under all conditions, nLD corresponded to a small population (2–10%) of total cellular LD. The anabolism triggered by OA, involving morphologic and size changes within the cLD and nLD populations, was reversed by a net balance of catabolism, upon eliminating OA. These catabolic processes included lipolysis and the mobilization of hydrolyzed FA from the LD to cytosolic-oxidation sites. These results would imply that nLD are actively involved in nuclear processes that include lipids. In conclusion, nLD are a dynamic nuclear domain since they are modified by OA through a reversible mechanism in combination with cLD; this process involves acyl-CoA-synthetase activity; ongoing TAG, CE, and PL biosynthesis. Thus, liver nLD and cLD are both dynamic cellular organelles.
Highlights
Nuclear-Lipid-Droplet Morphology Is Link with Lipid Methabolism structure: the nuclear bodies—such as the nucleolus, the Cajal body, speckles, premyelocytic leukemia, those being mainly composed by proteins and RNA [1]—and the nuclear lipid droplets that we have previously described and characterized under normal and nonpathologic conditions [2]. nLD have different morphologic characteristics and functional properties compared to nuclear bodies, since under nonpathologic conditions the nLD would be the only nuclear domain surrounded by a lipoprotein monolayer and mainly composed of lipids [2]
Under normal and nonpathologic conditions, nLD are a very small nuclear domain consisting of a few small lipid droplets (LD) randomly distributed within the nucleus that can be visualized only after staining. nLD are smaller and have a different proportion of the same neutrallipid classes than the cytoplasmic lipid droplets—i. e., polar lipids (PL) triacylglycerides (TAG), cholesterol esters (CE) and cholesterol (C) [2]. nLD have been observed in the nuclei of mice fed a high-fat diet [3] as well as under different pathologic conditions [4] such as in mouse embryos bearing a lethal mutation [5], in a liver patient with chronic hepatitis-C virus [6], and in carcinogen-fed rats [7] and mice [8]
Primary hepatocytes and HepG2 cells cultured under control physiologic conditions were analyzed by bright-field microscopy (S1 Fig) and confocal laser-scanning microscopy (Fig 2), for which latter visualization the nuclei were stained with DAPI and the LDs with BODIPY 493/503
Summary
In Eukaryotic cells the nucleus is a highly dynamic organelle where the processes of replication, transcription, RNA splicing, and ribosome assembly—among other fundamental cellular functions—take place.Within the nucleus, the nuclear matrix is circumscribed by the nuclear envelope and contains chromatin and two different types of domains, with the two having a specific supramolecularPLOS ONE | DOI:10.1371/journal.pone.0170608 January 26, 2017Nuclear-Lipid-Droplet Morphology Is Link with Lipid Methabolism structure: the nuclear bodies—such as the nucleolus, the Cajal body, speckles, premyelocytic leukemia, those being mainly composed by proteins and RNA [1]—and the nuclear lipid droplets (nLD) that we have previously described and characterized under normal and nonpathologic conditions [2]. nLD have different morphologic characteristics and functional properties compared to nuclear bodies, since under nonpathologic conditions the nLD would be the only nuclear domain surrounded by a lipoprotein monolayer and mainly composed of lipids [2].Under normal and nonpathologic conditions, nLD are a very small nuclear domain consisting of a few small lipid droplets (LD) randomly distributed within the nucleus that can be visualized only after staining. nLD are smaller and have a different proportion of the same neutrallipid classes than the cytoplasmic lipid droplets (cLD)—i. e., polar lipids (PL) triacylglycerides (TAG), cholesterol esters (CE) and cholesterol (C) [2]. nLD have been observed in the nuclei of mice fed a high-fat diet [3] as well as under different pathologic conditions [4] such as in mouse embryos bearing a lethal mutation [5], in a liver patient with chronic hepatitis-C virus [6], and in carcinogen-fed rats [7] and mice [8].nLD could be involved in nuclear-lipid homeostasis and serve as an endonuclear buffering system that would provide or incorporate lipids and proteins involved in signaling pathways, ligands for transcription factors, and enzymes catalyzing lipid metabolism and nuclear processes. NLD have different morphologic characteristics and functional properties compared to nuclear bodies, since under nonpathologic conditions the nLD would be the only nuclear domain surrounded by a lipoprotein monolayer and mainly composed of lipids [2]. Within the nucleus, the lipids would have two main locations: the nuclear envelope—composed mainly of glycerophospholipids, sphingolipids, and C—and the nLD (containing principally TAG, CE, C, and PL). Both of these domains would constitute alternative lipid sources with different chemical compositions, physical properties, potential functions, and possible regulatory characteristics
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