L-FABP facilitates nuclear oleic acid mobilization

LAYERENZA JUAN PABLO; LAGRUTTA L.C.; SISTI MARTIN SEBASTIAN; VES-LOSADA A.

Bari

Congreso; 54th International Conference on the Bioscience of Lipids: Linking Transcription to Physiology in Lipidomics(ICBL); 2013

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 abuffering system that provides and/or incorporates lipids of signaling pathways andtranscription factors.Taking into account that 18:0 and 20:4n-6 free or bound to L-FABP areincorporated into metabolic active N lipids pools by an acyl-CoA pathway, the aim ofthe present work was to determine the role of L-FABP in oleic acid (most abundantnLD fatty acid (FA)) mobilization and release. With this purpose: 1) N 18:1n-9 poolswere 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 atincreasing concentrations of delipidized L-FABP; 3) after incubation nLD wereisolated. Lipids were resolved by TLC and radioactivity quantified by scanning. Underthese conditions, 18:1n-9 was incorporated into N as FA and esterified toTAG>CE>GPL (glycerophospholipids) by an acyl-CoA mechanism; esterificationincreased with time and when18:1n-9 was L-FABP-bound. Increasing concentrations ofL-FABP determined a dose-dependent mobilization of N and nLD 18:1n-9 betweenTAG, CE, PE (glycerphosphoethanolamine), PC (glycerphosphocholine) and FA poolsas well as its release to the incubation medium.In conclusion, exogenous 18:1n-9 free or L-FABP bound is incorporated into Nand mainly esterified to TAG and CE nLD. Since L-FABP stimulates endonuclear 18:1mobilization, it may also deliver 18:1 to a nuclear acyl-CoA synthetase and then tothose enzymes responsible for its esterification in GPL, TAG and CE. At the same timeframe, L-FABP would mobilize 18:1n-9 to another fate, by promoting its release fromnLD pools to different cellular compartments.