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

Rachel A. Baar, Carlos S. Dingfelder, Lisa A. Smith, David A. Bernlohr, Chaodong Wu, Alex J. Lange, Elizabeth J. Parks

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87 Scopus citations

Abstract

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 litermates. 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.

Original languageEnglish (US)
Pages (from-to)E187-E193
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume288
Issue number1 51-1
DOIs
StatePublished - Jan 2005

Keywords

  • Adipocyte fatty acid-binding protein
  • Fatty acid turnover
  • Mouse model
  • Nonesterified fatty acids
  • Triacylglycerol

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