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J. Biol. Chem., Vol. 279, Issue 33, 34481-34488, August 13, 2004

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Heart Fatty Acid Uptake Is Decreased in Heart Fatty Acid-binding Protein Gene-ablated Mice^*

Eric J. Murphy, Gwendolyn Barcelo-Coblijn, Bert Binas¶, and Jan F. C. Glatz||**

From the Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, Grand Forks, North Dakota 58202-9037, the ^¶Department of Pathobiology, Texas A & M University, College Station, Texas 77843, and the ^||Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht 6200 MD, The Netherlands

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 heart fatty acid-binding protein (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]20:4n-6 compared with 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]20:4n-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]20:4n-6 entered each lipid pool measured, but these changes did not alter the distribution of tracer among these pools. In gene-ablated mice, significantly more [1-¹⁴C]16:0 was targeted to choline and ethanolamine glycerophospholipids, whereas more [1-¹⁴C]20:4n-6 was targeted to the phosphatidylinositol (PtdIns) pool. H-FABP gene ablation significantly increased PtdIns mass 1.4-fold but reduced PtdIns 20:4n-6 mass 30%. Consistent with a reported effect of FABP on plasmalogen mass, ethanolamine plasmalogen mass was reduced 30% in gene-ablated mice. Further, 20:4n-6 mass was reduced in each of the three other major phospholipid classes, suggesting H-FABP has a role in maintaining steady-state 20:4n-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.

Received for publication, December 29, 2003 , and in revised form, June 8, 2004.

^* This work was supported by American Heart Association Grant 0151121Z (to E. J. M.) and by a grant from the Netherlands Heart Foundation (to J. F. C. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** A Netherlands Heart Foundation Professor of Cardiac Metabolism.

To whom correspondence should be addressed: Dept. of Pharmacology, Physiology, and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Rd., Rm. 3700, Grand Forks, ND 58202-9037. Tel.: 701-777-3450; Fax: 701-777-4490; E-mail: emurphy{at}medicine.nodak.edu.

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