Department of Clinical Biochemistry, Jagiellonian University Medical College, Cracow, Poland.
J Physiol Pharmacol. 2010 Oct;61(5):607-18.
Mice with the knockout of endothelial nitric oxide synthase (eNOS ko) demonstrate symptoms resembling the human metabolic syndrome. NO has been recently demonstrated to be deeply involved in regulation of not only blood flow and angiogenesis, but also in modulation of mammalian basal energy substrate metabolism. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NOS. The enzyme dimethylarginine dimethylaminohydrolase (DDAH) catabolizes ADMA, what leads to increase of endogenous NO bioavailability. This study was aimed to compare the brown (BAT) and white (WAT) adipose tissue gene expression of age matched mice with decreased (eNOS ko) and increased (overexpressing DDAH) endogenous NO generation. The 19 week old eNOS ko mice demonstrated significantly lower weight, higher circulating glucose, insulin, leptin and cholesterol concentrations. The adiponectin as well as fasting triglyceride concentrations were not significantly altered. Animals with DDAH knock in, presented significantly increased angiogenic activity than eNOS ko mice. The microarray analysis pointed to activation of adipogenesis-related genes in eNOS ko mice in WAT, what was in contrast with the inhibition observed in the DDAH overexpressing mice. The angiogenesis related gene expression was down-regulated in both models in comparison to WT animals. This study support the multipotential role of endogenous NO in maintaining homeostasis of energy substrate catabolism.
敲除内皮型一氧化氮合酶（eNOS ko）的小鼠表现出类似于人类代谢综合征的症状。最近的研究表明，一氧化氮（NO）不仅参与了血流和血管生成的调节，还参与了哺乳动物基础能量底物代谢的调节。不对称二甲基精氨酸（ADMA）是一氧化氮合酶（NOS）的内源性竞争性抑制剂。酶二甲基精氨酸二甲氨基水解酶（DDAH）代谢 ADMA，导致内源性 NO 生物利用度增加。本研究旨在比较内源性 NO 生成减少（eNOS ko）和增加（DDAH 过表达）的年龄匹配小鼠的棕色（BAT）和白色（WAT）脂肪组织基因表达。19 周龄的 eNOS ko 小鼠体重明显降低，循环血糖、胰岛素、瘦素和胆固醇浓度升高。脂联素和空腹甘油三酯浓度没有明显改变。与 eNOS ko 小鼠相比，DDAH 敲入小鼠具有明显增加的血管生成活性。微阵列分析表明，在 WAT 中 eNOS ko 小鼠的脂肪生成相关基因被激活，而在 DDAH 过表达小鼠中则观察到抑制。与 WT 动物相比，两种模型的血管生成相关基因表达均下调。这项研究支持内源性 NO 在维持能量底物代谢平衡中的多能作用。
