Uncarboxylated Osteocalcin Increases Serum Nitric OxideLevels and Ameliorates Hypercholesterolemia in Mice Fed anAtherogenic Diet
Uncarboxylated Osteocalcin Increases Serum Nitric OxideLevels and Ameliorates Hypercholesterolemia in Mice Fed anAtherogenic Diet
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发表时间：
2017
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通讯作者：
A. Kondo;Tomoyo Kawakubo-Yasukochi;Akiko Mizokami;Sakura Chishaki;H. Takeuchi;M. Hirata
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作者：
A. Kondo;Tomoyo Kawakubo-Yasukochi;Akiko Mizokami;Sakura Chishaki;H. Takeuchi;M. Hirata
背景：骨钙素（OC）是一种成骨细胞衍生的骨基质蛋白，可能参与动脉粥样硬化的病理生理学。 OC 的生理作用以及在体内致动脉粥样硬化条件下 OC 给药的效果尚未得到研究。方法和结果：在这里，我们证明，对正常饮食或补充胆固醇和胆酸的饮食的野生型 C57BL/6 雌性小鼠进行急性或慢性非羧基化 OC (GluOC) 注射会导致血清一氧化氮 (NO) 水平升高。此外，我们的研究表明，GluOC 治疗导致白色脂肪组织和肝脏中肝脏 X 受体 α (LXRα)（胆固醇代谢中的关键转录因子）的表达水平升高，并改善了这些小鼠的高胆固醇血症。结论：因此，我们提出 GluOC 通过在野生型小鼠中产生血清 NO 和改善高胆固醇血症而表现出潜在的动脉粥样硬化保护作用。
Background: Osteocalcin (OC), an osteoblastderived bone matrix protein, may be involved in atherosclerosis pathophysiology. The physiological action of OC and the effect of OC administration under atherogenic conditions in vivo have not yet been examined. Methods and findings: Here we demonstrate that acute or Chronic Uncarboxylated OC (GluOC) injection in wild-type C57BL/6 female mice fed a normal diet or a diet supplemented with cholesterol and cholic acid resulted in increased serum Nitric Oxide (NO) levels. Furthermore, our study shows that GluOC treatment led to elevated expression levels of liver X receptor α (LXRα), a key transcription factor in cholesterol metabolism, in white adipose tissue and liver and ameliorated hypercholesteromia in those mice. Conclusion: We thus propose that GluOC exhibited potential atheroprotective effects through serum NO production and hypercholesterolemia improvement in wild-type mice.