Lipid metabolism and adipokine levels in fatty acid-binding protein null and transgenic mice
Lipid metabolism and adipokine levels in fatty acid-binding protein null and transgenic mice
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DOI：
10.1152/ajpendo.00465.2005
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发表时间：
2006-05-01
影响因子：
5.1
通讯作者：
Bernlohr, DA
中科院分区：
文献类型：
--
作者：
Hertzel, AV;Smith, LA;Bernlohr, DA
脂肪酸结合蛋白（FABPs）促进脂肪酸在细胞质内的扩散。与维持高脂肪饮食的C57B1/6J小鼠相比，脂肪- fabp （a - fabp）缺失小鼠表现出脂肪量增加、脂肪分解减少、肌肉葡萄糖氧化增加和胰岛素抵抗减弱，而脂肪组织中上皮- fabp （EFABP）的过度表达导致脂肪量减少、脂肪分解增加和胰岛素抵抗增强。为了确定这些过程背后的机制，实时PCR分析表明，相对于E-FABP过表达小鼠，A- fabp /aP2缺失小鼠中激素敏感脂肪酶的表达减少，而perilipin A的表达增加。相比之下，与E-FABP转基因动物相比，A-FABP/aP2阴性小鼠的新生脂肪生成和编码脂蛋白脂肪酶、CD36、长链酰基辅酶a合成酶5和二酰基甘油酰基转移酶的基因表达增加。与新生脂肪生成的增加一致，脂肪C16:0和C16:1酰基辅酶a库也增加了。血清游离脂肪酸在基因型之间没有变化。E-FABP转基因小鼠血清抵抗素水平降低，而A-FABP/ aP2阴性小鼠血清和组织脂联素水平升高，E-FABP转基因小鼠血清和组织脂联素水平降低；瘦素的表达不受影响。这些结果表明，在FABP缺失和转基因小鼠中，脂肪细胞中脂肪分解和脂肪生成之间的平衡被重塑，并伴随着脂肪细胞中脂肪因子表达的重编程和血浆脂肪因子的整体变化。
Fatty acid-binding proteins (FABPs) facilitate the diffusion of fatty acids within cellular cytoplasm. Compared with C57B1/6J mice maintained on a high-fat diet, adipose-FABP (A-FABP) null mice exhibit increased fat mass, decreased lipolysis, increased muscle glucose oxidation, and attenuated insulin resistance, whereas overexpression of epithelial-FABP (EFABP) in adipose tissue results in decreased fat mass, increased lipolysis, and potentiated insulin resistance. To identify the mechanisms that underlie these processes, real-time PCR analyses indicate that the expression of hormone-sensitive lipase is reduced, while perilipin A is increased in A-FABP/aP2 null mice relative to E-FABP overexpressing mice. In contrast, de novo lipogenesis and expression of genes encoding lipoprotein lipase, CD36, long-chain acyl-CoA synthetase 5, and diacylglycerol acyltransferase are increased in A-FABP/aP2 null mice relative to E-FABP transgenic animals. Consistent with an increase in de novo lipogenesis, there was an increase in adipose C16:0 and C16:1 acyl-CoA pools. There were no changes in serum free fatty acids between genotypes. Serum levels of resistin were decreased in the E-FABP transgenic mice, whereas serum and tissue adiponectin were increased in A-FABP/ aP2 null mice and decreased in E-FABP transgenic animals; leptin expression was unaffected. These results suggest that the balance between lipolysis and lipogenesis in adipocytes is remodeled in the FABP null and transgenic mice and is accompanied by the reprogramming adipokine expression in fat cells and overall changes in plasma adipokines.