Fèvre Cécile, Bellenger Sandrine, Pierre Anne-Sophie, Minville Mélaine, Bellenger Jérôme, Gresti Joseph, Rialland Mickaël, Narce Michel, Tessier Christian
INSERM UMR 866/Université de Bourgogne, Lipides Nutrition Cancer, Faculté des Sciences Gabriel, 6 Bd Gabriel, 21000 Dijon, France.
Biochim Biophys Acta. 2011 Jun;1811(6):409-17. doi: 10.1016/j.bbalip.2010.12.004. Epub 2010 Dec 21.
Metabolic syndrome characterized by insulin resistance and obesity is accompanied by severe lipid metabolism perturbations and chronic low-grade inflammation. However, many unresolved questions remained regarding the regulation that underlie dyslipidemia, particularly the regulation of the metabolic cascade (synthesis and release) leading to eicosanoid precursors release. This study was undertaken to investigate the regulation of desaturases/elongases and phospholipases A(2) during the establishment of metabolic syndrome. Our results showed that delta-6 desaturase as well as elongase-6 expressions were upregulated in 3-month-old Zucker fatty rats as compared to lean littermates, independently of SREBP-1c activation. We also demonstrated for the first time an increase of liver group VII phospholipase A(2) gene expression in the obese animals together with a strong specific inhibition of type IVA and VIA phospholipases A(2). These results suggest that the regulation of unsaturated fatty acids biosynthesis and signalling cascade could contribute to the development of liver lipid dysregulation related to metabolic syndrome and may be considered as new potential targets in such pathological conditions.
以胰岛素抵抗和肥胖为特征的代谢综合征伴有严重的脂质代谢紊乱和慢性低度炎症。然而，关于血脂异常背后的调节机制，尤其是导致类花生酸前体释放的代谢级联反应（合成和释放）的调节，仍存在许多未解决的问题。本研究旨在探讨代谢综合征发生过程中去饱和酶/延长酶和磷脂酶A2的调节机制。我们的结果表明，与瘦的同窝仔鼠相比，3月龄的Zucker肥胖大鼠中δ-6去饱和酶以及延长酶-6的表达上调，且与固醇调节元件结合蛋白-1c（SREBP-1c）的激活无关。我们还首次证明，肥胖动物肝脏VII组磷脂酶A2基因表达增加，同时IVA型和VIA型磷脂酶A2受到强烈的特异性抑制。这些结果表明，不饱和脂肪酸生物合成和信号级联反应的调节可能导致与代谢综合征相关的肝脏脂质失调的发展，并可能被视为这种病理状态下的新潜在靶点。
