Department of Clinical Biochemistry, Jagiellonian University Medical College, Kopernika 15a Street, 31-501 Cracow, Poland.
Cardiovasc Diabetol. 2011 Jul 22;10:68. doi: 10.1186/1475-2840-10-68.
High fat diet impairs nitric oxide (NO) bioavailability, and induces insulin resistance. The link between NO availability and the metabolic adaptation to a high fat diet is not well characterized. The purpose of this study was to investigate the effect of high fat diet on metabolism in mice with decreased (eNOS-/-) and increased (DDAH overexpressed) NO bioavailability.
eNOS-/- (n = 16), DDAH (n = 24), and WT (n = 19) mice were fed a high fat diet (HFD) for 13 weeks. Body weight, biochemical parameters, adipokines and insulin were monitored. The matrigel in vivo model with CD31 immunostaining was used to assess angiogenesis. Gene expression in adipose tissues was analyzed by microarray and Real Time PCR. Comparisons of the mean values were made using the unpaired Student t test and p < 0.05 were considered statistically significant.
eNOS-/- mice gained less weight than control WT and DDAH mice. In DDAH mice, a greater increase in serum adiponectin and a lesser increment in glucose level was observed. Fasting insulin and cholesterol levels remained unchanged. The angiogenic response was increased in DDAH mice. In adipose tissue of DDAH mice, genes characteristic of differentiated adipocytes were down-regulated, whereas in eNOS-/- mice, genes associated with adipogenesis, fatty acid and triglyceride synthesis were upregulated.
Our results indicate that increased NO availability attenuates some HFD induced alterations in metabolism and gene expression associated with insulin resistance.
高脂肪饮食会损害一氧化氮（NO）的生物利用度，并导致胰岛素抵抗。NO 生物利用度与代谢对高脂肪饮食适应之间的联系尚未得到很好的描述。本研究的目的是研究在 NO 生物利用度降低（eNOS-/-）和增加（DDAH 过表达）的小鼠中，高脂肪饮食对代谢的影响。
eNOS-/-（n = 16）、DDAH（n = 24）和 WT（n = 19）小鼠喂食高脂肪饮食（HFD）13 周。监测体重、生化参数、脂肪因子和胰岛素。使用 CD31 免疫染色的 Matrigel 体内模型评估血管生成。通过微阵列和实时 PCR 分析脂肪组织中的基因表达。使用未配对的 Student t 检验比较平均值，p < 0.05 被认为具有统计学意义。
与对照 WT 和 DDAH 小鼠相比，eNOS-/- 小鼠体重增加较少。在 DDAH 小鼠中，血清脂联素增加更多，血糖水平增加较少。空腹胰岛素和胆固醇水平保持不变。DDAH 小鼠的血管生成反应增强。在 DDAH 小鼠的脂肪组织中，与分化脂肪细胞特征相关的基因下调，而在 eNOS-/- 小鼠中，与脂肪生成、脂肪酸和甘油三酯合成相关的基因上调。
我们的结果表明，增加的 NO 可用性减轻了一些与胰岛素抵抗相关的 HFD 诱导的代谢和基因表达改变。
