Reversible Nuclear-Lipid-Droplet Morphology Induced by Oleic Acid: A Link to Cellular-Lipid Metabolism

Abstract

Neutral lipidsÐinvolved in many cellular processesÐare stored as lipid droplets (LD), thosemainly cytosolic (cLD) along with a small nuclear population (nLD). nLD could be involved innuclear-lipid homeostasis serving as an endonuclear buffering system that would provide orincorporate lipids and proteins involved in signalling pathways as transcription factors andas enzymes of lipid metabolism and nuclear processes. Our aim was to determine if nLDconstituted a dynamic domain. Oleic-acid (OA) added to rat hepatocytes or HepG2 cells inculture produced cellular-phenotypic LD modifications: increases in TAG, CE, C, and PLcontent and in cLD and nLD numbers and sizes. LD increments were reversed on exclusionof OA and were prevented by inhibition of acyl-CoA synthetase (with Triacsin C) and thuslipid biosynthesis. Under all conditions, nLD corresponded to a small population (2±10%) oftotal cellular LD. The anabolism triggered by OA, involving morphologic and size changeswithin the cLD and nLD populations, was reversed by a net balance of catabolism, uponeliminating OA. These catabolic processes included lipolysis and the mobilization of hydrolyzedFA from the LD to cytosolic-oxidation sites. These results would imply that nLD areactively involved in nuclear processes that include lipids. In conclusion, nLD are a dynamicnuclear domain since they are modified by OA through a reversible mechanism in combinationwith cLD; this process involves acyl-CoA-synthetase activity; ongoing TAG, CE, and PLbiosynthesis. Thus, liver nLD and cLD are both dynamic cellular organelles.