Investigation of in vivo fatty acid metabolism in AFABP/aP2(-/-) mice.
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.
Baar
Rachel A
RA
Department of Food Science and Nutrition, University of Minnesota, 1334 Eckles Ave., St. Paul, MN 55108, USA.
Dingfelder
Carlus S
CS
Smith
Lisa A
LA
Bernlohr
David A
DA
Wu
Chaodong
C
Lange
Alex J
AJ
Parks
Elizabeth J
EJ
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002153:Calorimetry, Indirect; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004041:Dietary Fats / Q000493:pharmacokinetics; D004734:Energy Metabolism / Q000502:physiology; D005215:Fasting / Q000502:physiology; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014280:Triglycerides / Q000378:metabolism
D002352:Carrier Proteins; D004041:Dietary Fats; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides