Targeted disruption of the adipocyte lipid-binding protein (aP2 protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels

The availability of mice containing an adipocyte lipid-binding protein (ALB P/aP2) gene disruption allowed for a direct examination of the presumed rol e of lipid-binding proteins iu the mobilization and trafficking of intracel lular fatty acids. Total body and epididymal fat pad weights, as well as ad ipose cell morphology, were unaltered in male ALBP/aP2 disrupted mice when compared to their wild-type littermates, Analysis of adipocytes isolated fr om wild-type and ALBP/aP2 null mice revealed that a selective 40- and 13-fo ld increase in the level of the keratinocyte lipid-binding protein (KLBP) m RNA and protein, respectively, accompanied the ALBP/aP2 gene disruption, Al though KLBP protein was significantly up-regulated, the total lipid-binding protein level decreased 8-fold as a consequence of the disruption. There w as no appreciable difference in the rate of fatty acid influx or esterifica tion in adipocytes of wild-type and ALBP/aP2 null animals, To the contrary basal lipolysis decreased approximately 40% in ALBP/aP2 nulls as compared t o wild-type littermates. The glycerol release from isproterenol-stimulated ALBP/aP2 null fat cells was similarly reduced by similar to 35%. Consistent with a decrease in basal efflux, the non-esterified fatty acid (NEFA) leve l was nearly 3-fold greater iu adipocytes from ALBP/aP2 nulls as compared t o wild-type animals. The significant decrease in both basal and isoproteren ol-stimulated lipolysis in adipose tissue of ALBP/aP2 null mice supports th e model whereby intracellular lipid-binding proteins function as lipid chap erones, facilitating the movement of fatty acids out of the fat cell.