Adipocyte metabolism in adipocyte fatty acid binding protein knockout (aP2(-/-)) mice after short-term high-fat feeding - Functional compensation by the keritinocyte fatty acid binding protein

Mice null for adipocyte fatty acid binding protein (AFABP) compensate by in creasing expression of keratinocyte fatty acid binding protein (KFABP) (Hot amisligil et al. Science 274:1377-1379, 1996). In the present study, AFABP knockout (KO) and wild-type (WT) mice became equally obese on a high-fat di et., as judged by fat pad weights, adipocyte size, and body composition ana lysis. High-fat feeding led to moderate insulin resistance in both WT and A FABP knockout mice, as indicated by an similar to 2-fold increase in plasma insulin. However, in the high fat-fed mice, plasma glucose levels were sim ilar to 15% lower in the AFABP-KO mice. Adipocytes isolated from AFABP-KO a nd WT mice fed high- or low-fat diets exhibited similar rates of basal and norepinephrine-stimulated lipolysis and insulin-stimulated rates of glucose conversion to fatty acids and glyceride-glycerol. However basal glucose co nversion to fatty acids was higher in adipocytes of AFABP-KO mice. Adipocyt e tumor necrosis factor-alpha release was similarly increased by high-fat d iet-induced obesity in both WT and AFABP-KO mice. As assessed by Western bl ot analysis, the level of KFABP protein in AFABP-KOs was similar to 40% of the level of AFABP in WT controls. The binding affinities of KFABP for long -chain fatty acids were 2- to 4-fold higher than those of AFABP, but the re lative affinities for different fatty acids were similar. As for AFABP, the rate of fatty acid transfer from KFABP to model phospholipid vesicles was increased with acceptor membrane concentration and by inclusion of acidic p hospholipids, indicating a similar mechanism of transfer. We conclude KFABP can functionally compensate for the absence of KFABP, resulting in no majo r alterations in adipocyte metabolism or fat accumulation in response to sh ort-term feeding of high-fat diets that result, in moderate hyper-insulinem ia.