L-FABP facilitates nuclear oleic acid mobilization

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

Bari

Congreso; 54th International Conference on the Biochemistry of lipids", ICBL; 2013

International Conference on the Biochemistry of lipids", ICBL

Nuclear (N) lipids are located in nuclear membranes and Nuclear Lipid Droplets (nLD) (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 present work was to determine the role of L-FABP in oleic acid (most abundant nLD fatty acid (FA)) mobilization and release. With this purpose: 1) N 18:1n-9 pools were labeled (N*) in vitro incubating N with [1-14C]18:1n-9 free or L-FABP-bound, ATP and CoA; 2) N* were incubated without 18:1, though plus ATP and CoA at increasing concentrations of delipidized 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.