Targeted disruption of the adipocyte lipid-binding protein (aP2 protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels.
Targeted disruption of the adipocyte lipid-binding protein (aP2 protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels.
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发表时间：
1999-05
影响因子：
6.5
通讯作者：
N. R. Coe;Melanie A. Simpson;D. Bernlohr
中科院分区：
文献类型：
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作者：
N. R. Coe;Melanie A. Simpson;D. Bernlohr
含有脂肪细胞脂质结合蛋白（ALBP/aP 2）基因破坏的小鼠的可用性允许直接检查脂质结合蛋白在细胞内脂肪酸的动员和运输中的假定作用。与野生型同窝小鼠相比，雄性ALBP/aP 2破坏小鼠的总体重和附睾脂肪垫重量以及脂肪细胞形态未发生变化。从野生型和ALBP/aP 2基因敲除小鼠中分离的脂肪细胞的分析显示，角质形成细胞脂质结合蛋白（KLBP）mRNA和蛋白质水平分别选择性增加40倍和13倍，伴随着ALBP/aP 2基因的破坏。虽然KLBP蛋白显著上调，但总脂质结合蛋白水平由于破坏而降低了8倍。野生型和ALBP/aP 2缺失动物的脂肪细胞中脂肪酸流入或酯化率没有明显差异。相反，与野生型同窝仔相比，ALBP/aP 2无效的基础脂解降低约40%。从异丙肾上腺素刺激的ALBP/aP 2无效脂肪细胞的甘油释放类似地减少约35%。与基础外排减少一致，与野生型动物相比，来自ALBP/aP 2无效的脂肪细胞中的非酯化脂肪酸（NEFA）水平几乎高3倍。ALBP/aP 2基因敲除小鼠脂肪组织中基础和异丙肾上腺素刺激的脂解作用均显著降低，这支持了细胞内脂质结合蛋白作为脂质伴侣发挥作用，促进脂肪酸从脂肪细胞中移出的模型。
The availability of mice containing an adipocyte lipid-binding protein (ALBP/aP2) gene disruption allowed for a direct examination of the presumed role of lipid-binding proteins in the mobilization and trafficking of intracellular fatty acids. Total body and epididymal fat pad weights, as well as adipose cell morphology, were unaltered in male ALBP/aP2 disrupted mice when compared to their wild-type littermates. Analysis of adipocytes isolated from wild-type and ALBP/aP2 null mice revealed that a selective 40- and 13-fold increase in the level of the keratinocyte lipid-binding protein (KLBP) mRNA and protein, respectively, accompanied the ALBP/aP2 gene disruption. Although KLBP protein was significantly up-regulated, the total lipid-binding protein level decreased 8 -fold as a consequence of the disruption. There was no appreciable difference in the rate of fatty acid influx or esterification in adipocytes of wild-type and ALBP/aP2 null animals. To the contrary, basal lipolysis decreased approximately 40% in ALBP/aP2 nulls as compared to wild-type littermates. The glycerol release from isproterenol-stimulated ALBP/aP2 null fat cells was similarly reduced by approximately 35%. Consistent with a decrease in basal efflux, the non-esterified fatty acid (NEFA) level was nearly 3-fold greater in adipocytes from ALBP/aP2 nulls as compared to wild-type animals. The significant decrease in both basal and isoproterenol-stimulated lipolysis in adipose tissue of ALBP/aP2 null mice supports the model whereby intracellular lipid-binding proteins function as lipid chaperones, facilitating the movement of fatty acids out of the fat cell.