From the Departments of Internal Medicine (C.M.L., D.A.K., F.M.F.) and Pharmacology (F.M.F.), The University of Iowa Carver College of Medicine, Iowa City, IA; Vascular Biology Center (X.C., E.M.) and Department of Physiology, Medical College of Georgia (J.F., A.E.), Georgia Regents University, Augusta, GA; Departments of Pharmacology (S.Z., J.L.F., S.P.D.) and Neurology (S.P.D.), The University of Mississippi Medical Center, Jackson, MS; and Charlie Norwood VA Medical Center, Augusta, GA (A.E.).
Stroke. 2013 Nov;44(11):3195-201. doi: 10.1161/STROKEAHA.113.001366. Epub 2013 Sep 26.
Obesity is an increasing epidemic worldwide; however, little is known about effects of obesity produced by high-fat diet (HFD) on the cerebral circulation. The purpose of this study was to examine the functional and temporal effects of a HFD on carotid and cerebral vascular function and to identify mechanisms that contribute to such functional alterations.
Responses of cerebral arterioles (in vivo) and carotid arteries (in vitro) were examined in C57Bl/6 (wild-type) and Nox2-deficient (Nox2(-/-)) mice fed a control (10%) or a HFD (45% or 60% kcal of fat) for 8, 12, 30, or 36 weeks.
In wild-type mice, a HFD produced obesity and endothelial dysfunction by 12 and 36 weeks in cerebral arterioles and carotid arteries, respectively. Endothelial function could be significantly improved with Tempol (a superoxide scavenger) treatment in wild-type mice fed a HFD. Despite producing a similar degree of obesity in both wild-type and Nox2(-/-) mice, endothelial dysfunction was observed only in wild-type, but not in Nox2(-/-), mice fed a HFD.
Endothelial dysfunction produced by a HFD occurs in a temporal manner and appears much earlier in cerebral arterioles than in carotid arteries. Genetic studies revealed that Nox2-derived superoxide plays a major role in endothelial dysfunction produced by a HFD. Such functional changes may serve to predispose blood vessels to reduced vasodilator responses and thus may contribute to alterations in cerebral blood flow associated with obesity.
肥胖是全球日益严重的流行疾病，但对于高脂肪饮食（HFD）引起的肥胖对脑循环的影响知之甚少。本研究旨在研究 HFD 对颈动脉和脑血管功能的功能和时间影响，并确定导致这种功能改变的机制。
在 C57Bl/6（野生型）和 Nox2 缺陷型（Nox2(-/-)）小鼠中检查脑小动脉（体内）和颈动脉（体外）的反应，这些小鼠分别喂食对照（10%）或 HFD（45%或 60%的脂肪卡路里）8、12、30 或 36 周。
在野生型小鼠中，HFD 在 12 周和 36 周时分别在脑小动脉和颈动脉中引起肥胖和内皮功能障碍。在 HFD 喂养的野生型小鼠中，Tempol（一种超氧化物清除剂）治疗可显著改善内皮功能。尽管在野生型和 Nox2(-/-)小鼠中产生了相似程度的肥胖，但仅在 HFD 喂养的野生型小鼠中观察到内皮功能障碍，而在 Nox2(-/-)小鼠中未观察到。
HFD 引起的内皮功能障碍呈时间依赖性，在脑小动脉中比在颈动脉中更早出现。遗传研究表明，Nox2 衍生的超氧化物在 HFD 引起的内皮功能障碍中起主要作用。这种功能变化可能使血管容易出现血管扩张剂反应降低，从而可能导致与肥胖相关的脑血流改变。
