Increased lipolysis in transgenic animals overexpressing the epithelial fatty acid binding protein in adipose cells
Increased lipolysis in transgenic animals overexpressing the epithelial fatty acid binding protein in adipose cells
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DOI：
10.1194/jlr.m200227-jlr200
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发表时间：
2002-12-01
影响因子：
6.5
通讯作者：
Bernlohr, DA
中科院分区：
文献类型：
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作者：
Hertzel, AV;Bennaars-Eiden, A;Bernlohr, DA
脂肪酸结合蛋白（Fatty acid binding proteins，FABPs）是一类低分子量、可溶性的细胞内脂质载体。先前对来自脂肪细胞脂肪酸结合蛋白（A-FABP）缺陷小鼠的脂肪细胞的研究表明，基础和异丙肾上腺素刺激的脂解作用均显著降低（Coe et al. 1999. 40：967-972）。在此，我们报告的FABP 5基因编码的上皮脂肪酸结合蛋白（E-FABP）在脂肪细胞中过表达的转基因小鼠的建设，从而允许脂肪分解的影响，增加FABP水平和类型特异性的评估。在来自FABP 5转基因小鼠的脂肪细胞中，与野生型相比，脂肪细胞中的总FABP蛋白水平增加至150%，这是由于E-FABP水平增加10倍和A-FABP的未预料到的2倍下调。野生型和FABP 5转基因小鼠之间的体重、血清FFA或脂肪垫质量没有显著差异。重要的是，FABP 5转基因动物的脂肪细胞中基础和脂肪酶刺激的脂解作用均增加。无论是从细胞内室或从脂肪细胞流出的脂肪酸池的分子组成是不变的。这些结果表明，脂肪分解与总FABP水平之间存在正相关，但脂肪分解与特定FABP类型之间不存在正相关。
Fatty acid binding proteins (FABPs) are low-molecular-mass, soluble, intracellular lipid carriers. Previous studies on adipocytes from adipocyte fatty acid binding protein (A-FABP)-deficient mice have revealed that both basal and isoproterenol-stimulated lipolysis were markedly reduced (Coe et al. 1999. J Lipid Res. 40: 967-972). Herein, we report the construction of transgenic mice overexpressing the FABP5 gene encoding the epithelial fatty acid binding protein (E-FABP) in adipocytes, thereby allowing evaluation of the effects on lipolysis of increased FABP levels and of type specificity. In adipocytes from FABP5 transgenic mice, the total FABP protein level in the adipocyte was increased to 150% as compared to the wild type due to a 10-fold increase in the level of E-FABP and an unanticipated 2-fold down-regulation of the A-FABP. There were no significant differences in body weight, serum FFA, or fat pad mass between wild-type and FABP5 transgenic mice. Importantly, both basal and hormone-stimulated lipolysis increased in adipocytes from the FABP5 transgenic animals. The molecular composition of the fatty acid pool from either the intracellular compartment or that effluxed from the adipocyte was unaltered. These results demonstrate that there is a positive relationship between lipolysis and the total level of FABP but not between lipolysis and a specific FABP type.