Differential Regulation of Dihydroceramide Desaturase by Palmitate versus Monounsaturated Fatty Acids IMPLICATIONS FOR INSULIN RESISTANCE
Differential Regulation of Dihydroceramide Desaturase by Palmitate versus Monounsaturated Fatty Acids IMPLICATIONS FOR INSULIN RESISTANCE
复制标题
DOI：
10.1074/jbc.m110.186916
复制
发表时间：
2011-05-13
影响因子：
4.8
通讯作者：
Cowart, L. Ashley
中科院分区：
文献类型：
--
作者：
Hu, Wei;Ross, Jessica;Cowart, L. Ashley
许多数据表明饱和脂肪酸与肥胖、糖尿病和代谢综合征相关的有害过程有关。当饱和脂肪酸对组织的可用性增加时，许多这些变化可能是由于生物活性脂质的异常产生。另一方面，越来越多的研究表明，单不饱和脂肪酸油酸酯可以防止饱和脂肪介导的毒性；然而，其机制尚不清楚。我们的数据表明棕榈酸酯在增加DES1 mRNA编码中的新作用，DES1是负责从其前体二氢神经酰胺生成神经酰胺的酶，从而控制生物活性脂质神经酰胺的合成。此外，与油酸酯共处理可以抑制神经酰胺的增加，这是通过抑制DES1信息和活性的增加来实现的。DES1的敲低也可以保护棕榈酸盐诱导的胰岛素抵抗，而该酶的过表达可以改善油酸盐的保护作用。总之，这些发现为油酸介导的代谢性疾病保护机制提供了新的见解，并为脂肪酸介导的神经酰胺生物合成关键酶的调节提供了新的证据。
Much data implicate saturated fatty acids in deleterious processes associated with obesity, diabetes, and the metabolic syndrome. Many of these changes may be due to aberrant generation of bioactive lipids when saturated fatty acid availability to tissues is increased. On the other hand, studies are emerging that implicate the monounsaturated fatty acid oleate in protection from saturated fat mediated toxicity; however, the mechanisms are not well understood. Our data demonstrate a novel role for palmitate in increasing mRNA encoding DES1, which is the enzyme responsible for generating ceramide from its precursor dihydroceramide and thus controls synthesis of the bioactive lipid ceramide. Moreover, co-treatment with oleate prevented the increase in ceramide, and this occurred through attenuation of the increase in message and activity of DES1. Knockdown of DES1 also protected from palmitate-induced insulin resistance, and overexpression of this enzyme ameliorated the protective effect of oleate. Together, these findings provide insight into the mechanisms of oleate-mediated protection against metabolic disease and provide novel evidence for fatty acid-mediated regulation of a key enzyme of ceramide biosynthesis.