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Papers In Press, published online ahead of print June 11, 2004
J. Biol. Chem, 10.1074/jbc.M314263200
Submitted on December 29, 2003
Revised on June 8, 2004
Accepted on June 11, 2004

Heart fatty acid uptake is decreased in heart-fatty acid binding protein gene-ablated mice

Eric J. Murphy, Gwedolyn Barcelo-Coblijn, Bert Binas, and Jan F. C. Glatz

Pharmacology, Physiology, and Therapeutics, University of North Dakota, Grand Forks, ND 58202-9037

Corresponding Author: emurphy{at}medicine.nodak.edu

Cell culture systems have demonstrated a role for cytoplasmic fatty acid binding proteins (FABP) in lipid metabolism, although a similar function in intact animals is unknown. We addressed this issue using H-FABP gene-ablated mice. H-FABP gene ablation reduced total heart fatty acid uptake 40% and 52% for [1-14C]16:0 and [1-14C]20:4 n-6 compared to controls, respectively. Similarly, the amount of fatty acid found in the aqueous fraction was reduced 40% and 52% for [1-14C]16:0 and [1-14C]20:4 n-6, respectively. Less [1-14C]16:0, entered the triacylglycerol pool, with significant redistribution of fatty acid between the triacylglycerol pool and the total phospholipid pool. Less [1-14C]20:4 n-6,entered each lipid pool measured, but these changes did not alter the distribution of tracer amongst these pools. In gene-ablated mice, significantly more [1-14C]16:0 was targeted to choline and ethanolamine glycerophospholipids, while more [1-14C]20:4 n-6 was targeted to the phosphatidyinositiol(PtdIns) pool. H-FABP gene ablation significantly increased PtdIns mass 1.4-fold, but reduced PtdIns 20:4 n-6 mass 30%. Consistent with a reported effect of FABP on plasmalogen mass, ethanolamine plasmalogen (PlsEtn) mass was reduced 30% in gene-ablated mice. Further, 20:4 n-6 mass was reduced in each of the three other major phospholipid classes, suggesting H-FABP has a role in maintaining steady-state 20:4 n-6 mass in heart. In summary, H-FABP was important for heart fatty acid uptake and targeting of fatty acids to specific heart lipid pools as well as for maintenance of phospholipid pool mass and acyl chain composition.


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