Nuclear oleic acid mobilization is promoted by L-FABP

LAYERENZA, JUAN P.; LAGRUTTA, LUCÍA C.; SISTI MARTÍN S.; VES LOSADA, ANA

Congreso; 8th International Conference of Lipid Binding Proteins (LBP); 2013

International Conference of Lipid Binding Proteins (ICLBP)

The cell nucleus (N) is a highly compartmentalized organelle characterized by several dynamic domains. We have already shown that nuclear lipid droplets (nLD) are a new class of subnuclear bodies and a nuclear domain where neutral lipids are stored and organized (mainly composed of TAG (triacylglycerols), CE (cholesteryl esters) and C (cholesterol). nLD could be involved in N lipid homeostasis and may serve as a buffering system that provides and/or incorporates lipids of signaling pathways and transcription factors. Taking into account that 18:0 and 20:4n-6 free or bound to L-FABP are incorporated into metabolic active N lipids pools by an acyl-CoA pathway, the aim of the work was to determine L-FABP role in oleic acid (most abundant nLD fatty acid (FA)) mobilization and release. With this purpose: 1) N 18:1n-9 pools were labeled (N*) incubating N with [1-14C] 18:1n-9 free or L-FABP-bound, ATP and CoA; 2) N* were incubated without 18:1, plus ATP, CoA and L-FABP; 3) after incubation nLD were isolated. Lipids were resolved by TLC and radioactivity quantified by scanning. Under these conditions, 18:1n-9 was incorporated into N as FA and esterified to TAG>CE>GPL (glycerophospholipids) by an acyl-CoA mechanism; esterification increased with time and when18:1n-9 was L-FABP-bound. Increasing concentrations of L-FABP determined a dose-dependent mobilization of N and nLD 18:1n-9 between TAG, CE, PE (glycerphosphoethanolamine), PC (glycerphosphocholine) and FA pools as well as its release to the incubation medium. In conclusion, exogenous 18:1n-9 free or L-FABP bound is incorporated into N and mainly esterified to TAG and CE nLD. Since L-FABP stimulates endonuclear 18:1 mobilization, it may also deliver 18:1 to a nuclear acyl-CoA synthetase and then to those enzymes responsible for its esterification in GPL, TAG and CE. At the same time frame, L-FABP would mobilize 18:1n-9 to another fate, by promoting its release from nLD pools to different cellular compartments.