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Investigation of in vivo fatty acid metabolism in AFABP/aP2^–/– mice

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

Submitted 15 June 2004 ; accepted in final form 3 September 2004

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 with wild-type C57BL/6J littermates. Mice were weaned on a high-fat diet (59% of energy from fat) and acclimated to meal feeding. Stable isotopes were administered, and indirect calorimetry was performed to quantitate fatty acid flux, dietary fatty acid utilization, and substrate oxidation. Consistent with previous in situ and in vitro studies, fasting serum nonesterified fatty acid (NEFA) release was significantly reduced in AFABP/aP2^–/– (17.1 ± 9.0 vs. 51.9 ± 22.9 mg·kg^–1·min^–1). AFABP/aP2^–/– exhibited higher serum NEFA (1.4 ± 0.6 vs. 0.8 ± 0.4 mmol/l, AFABP/aP2^–/– vs. C57BL/6J, respectively) and 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 wt) 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 that in vivo disruption of AFABP/aP2^–/– leads to changes in the following two major metabolic processes: 1) decreased adipose NEFA efflux and 2) preferential utilization of glucose relative to fatty acids.

adipocyte fatty acid-binding protein; fatty acid turnover; triacylglycerol; nonesterified fatty acids; mouse model

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