Adipocyte Metabolism in Adipocyte Fatty Acid Binding Protein Knockout (aP2

Mice null for adipocyte fatty acid binding protein ( A FABP) compensate by increasing expression of keratinocyte fatty acid binding protein (KFABP) (Hotamisligil et al. S c i e n c e 274:1377–1379, 1996). In the present s t u d y, AFABP knockout (KO) and wild-type (WT) mice became equally obese on a high-fat diet, as judged by fat pad weights, adipocyte size, and body composition analysis. High-fat feeding led to moderate insulin resistance in both WT and AFABP knockout mice, as indicated by an ~2-fold increase in plasma insulin. H o w e v e r, in the high fat–fed mice, plasma glucose levels were ~15% lower in the AFABP-KO mice. Adipocytes isolated from AFABP-KO and WT mice fed highor low-fat diets exhibited similar rates of basal and norepinephrine-stimulated lipolysis and insulinstimulated rates of glucose conversion to fatty acids and glyceride-glycerol. However, basal glucose conversion to fatty acids was higher in adipocytes of AFA B P KO mice. Adipocyte tumor necrosis factorr e l e a s e was similarly increased by high-fat diet–induced obesity in both WT and AFABP-KO mice. As assessed by We s tern blot analysis, the level of KFABP protein in A FABP-KOs was ~40% of the level of AFABP in WT controls. The binding affinities of KFABP for longchain fatty acids were 2to 4-fold higher than those of A FA B P, but the relative affinities for different fatty acids were similar. As for AFA B P, the rate of fatty acid transfer from KFABP to model phospholipid vesicles was increased with acceptor membrane concentration and by inclusion of acidic phospholipids, indicating a similar mechanism of transfer. We conclude KFABP can functionally compensate for the absence of AFA B P, resulting in no major alterations in adipocyte metabolism or fat accumulation in response to short-term feeding of high-fat diets that result in moderate hyperinsulinemia. D i a b e t e s 4 9 :9 0 4–911, 2000