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Am J Physiol Endocrinol Metab (September 14, 2004). doi:10.1152/ajpendo.00256.2004
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Submitted on June 15, 2004
Accepted on September 3, 2004

Investigation of in vivo fatty acid metabolism in AFABP/aP2-/- mice

Rachel A. Baar1, Carlus S. Dingfelder1, Lisa A. Smith2, Dave A. Bernlohr2, Chaodong Wu2, Alex J. Lange2, and Elizabeth J. Parks1*

1 Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN, USA
2 Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA

* To whom correspondence should be addressed. E-mail: eparks{at}umn.edu.

The metabolic impact of the murine adipocyte fatty acid binding protein (AFABP/aP2) on lipid metabolism was investigated in the AFABP/aP2-/- mouse and compared to wild type C57Bl/6J littermates. Mice weaned on a high-fat diet (59% of energy from fat) and acclimated to meal feeding. Stable isotopes were administered and indirect calorimetry performed to quantitate fatty acid flux, dietary fatty acid utilization, and substrate oxidation. Consistent with previous in situ and in vitro studies, fasting serum non-esterified fatty acids (NEFA) release was significantly reduced in AFABP/aP2-/- (17.1 ± 9.0 vs 51.9 ± 22.9 mg/kg/min). AFABP/aP2-/- exhibited higher serum NEFA (1.4 ± 0.6 vs 0.8 ± 0.4 mmol/L, AFABP/aP2-/- vs C57Bl/6J, respectively), triacylglycerol (TAG) (0.23 ± 0.09 vs 0.13 ± 0.10 mmol/L), and accumulated more TAG in liver tissue (2.9 ± 2.3 vs 1.1 ± 0.8 % wet weight) in the fasted state. For the liver-TAG pool, 16.4 ± 7.3% of TAG-fatty acids were derived from serum NEFA in AFABP/aP2-/-. In contrast, a significantly greater portion of C57Bl/6J liver-TAG was derived from serum NEFA (42.3 ± 25.5%) during tracer infusion. For adipose-TAG stores, only 0.29 ± 0.04% was derived from serum NEFA in AFABP/aP2-/-, and in C57Bl/6J, 1.85 ± 0.97% of adipose-TAG was derived from NEFA. In addition, AFABP/aP2-/- preferentially oxidized glucose relative to fatty acids in the fed state. These data demonstrate in vivo disruption of AFABP/aP2-/- leads to changes in two major metabolic processes; 1) decreased adipose NEFA efflux and 2) preferential utilization of glucose relative to fatty acids.




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