title: Loss of intracellular lipid binding proteins differentially impacts saturated fatty acid uptake and nuclear targeting in mouse hepatocytes.
abstract: The liver expresses high levels of two proteins with high affinity for long-chain fatty acids (LCFAs): liver fatty acid binding protein (L-FABP) and sterol carrier protein-2 (SCP-2). Real-time confocal microscopy of cultured primary hepatocytes from gene-ablated (L-FABP, SCP-2/SCP-x, and L-FABP/SCP-2/SCP-x null) mice showed that the loss of L-FABP reduced cellular uptake of 12-N-methyl-(7-nitrobenz-2-oxa-1,3-diazo)-aminostearic acid (a fluorescent-saturated LCFA analog) by ∼50%. Importantly, nuclear targeting of the LCFA was enhanced when L-FABP was upregulated (SCP-2/SCP-x null) but was significantly reduced when L-FABP was ablated (L-FABP null), thus impacting LCFA nuclear targeting. These effects were not associated with a net decrease in expression of key membrane proteins involved in LCFA or glucose transport. Since hepatic LCFA uptake and metabolism are closely linked to glucose uptake, the effect of glucose on L-FABP-mediated LCFA uptake and nuclear targeting was examined. Increasing concentrations of glucose decreased cellular LCFA uptake and even more extensively decreased LCFA nuclear targeting. Loss of L-FABP exacerbated the decrease in LCFA nuclear targeting, while loss of SCP-2 reduced the glucose effect, resulting in enhanced LCFA nuclear targeting compared with control. Simply, ablation of L-FABP decreases LCFA uptake and even more extensively decreases its nuclear targeting.
authors.affiliation: Department of Physiology and Pharmacology, Texas A & M University, TVMC, College Station, TX 77843-4466, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Storey
authors.forename: Avery L
authors.initials: AL
authors.lastname: McIntosh
authors.forename: Huan
authors.initials: H
authors.lastname: Huang
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Martin
authors.forename: Kerstin K
authors.initials: KK
authors.lastname: Landrock
authors.forename: Danilo
authors.initials: D
authors.lastname: Landrock
authors.forename: H Ross
authors.initials: HR
authors.lastname: Payne
authors.forename: Ann B
authors.initials: AB
authors.lastname: Kier
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Schroeder
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000502:physiology*; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D013229:Stearic Acids / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D008565:Membrane Proteins; D013229:Stearic Acids; C072087:sterol carrier proteins; D005947:Glucose