Naderali Ebrahim K, Fatani Sameer, Williams Gareth
Neuroendocrine and Obesity Biology Unit, Department of Medicine, University of Liverpool, Daulby Street, Liverpool L69 3GA, UK.
Atherosclerosis. 2004 Dec;177(2):307-12. doi: 10.1016/j.atherosclerosis.2004.07.029.
In humans, dietary-induced obesity markedly increases plasma lipid profile and impairs vascular function leading to increased incidence of cardiovascular events. We have recently reported that chronic withdrawal of obesity-inducing diet attenuates obesity and completely corrects endothelial function. The aim of this study was to investigate whether fenofibrate-induced decrease in adiposity would also correct vascular function in the presence of obesity-inducing diet. Wistar rats were fed with either standard laboratory chow (lean, n = 9) or given a highly palatable diet (diet-fed, n = 18) for 15 weeks. After 7 weeks, half of the diet-fed group was treated with fenofibrate (fenofibrate-treated, n = 9) for 8 weeks before being sacrificed. Untreated diet-fed (n = 9) rats had significantly higher body weight, total fat mass (by up to two-fold, p < 0.001 for both), and raised fasting plasma levels of insulin, leptin and triglycerides (up to 110%; p < 0.001), but not glucose or nonesterified fatty acids (NEFA) than both lean control and fenofibrate-treated groups. Resistance mesenteric arteries responses to KCl- and noradrenaline-induced vasoconstriction were similar in all three groups. However, compared with lean controls, endothelium-dependent vasorelaxation responses were shifted to the right in both untreated and fenofibrate-treated diet-fed groups. Fenofibrate treatment improved endothelium-dependent vasorelaxation at only high carbamycholine concentrations (10 microM). There were no differences in endothelium-independent vasorelaxation between the three groups. These results indicate that, in the presence of obesity-inducing diet, fenofibrate markedly reverses obesity and corrects insulin resistance and lipid profile, but it only has a limited beneficial effect on vascular function. Therefore, it seems that diet component rather than obesity per se plays a key role in the genesis of vascular abnormalities.
在人类中，饮食诱导的肥胖显著增加血浆脂质水平并损害血管功能，导致心血管事件的发生率增加。我们最近报道，长期停用致肥胖饮食可减轻肥胖并完全纠正内皮功能。本研究的目的是调查在存在致肥胖饮食的情况下，非诺贝特诱导的肥胖减轻是否也能纠正血管功能。将Wistar大鼠分为两组，一组喂食标准实验室饲料（瘦鼠，n = 9），另一组给予美味饲料（饮食喂养组，n = 18），持续15周。7周后，饮食喂养组的一半大鼠（非诺贝特治疗组，n = 9）接受非诺贝特治疗8周，然后处死。未治疗的饮食喂养组（n = 9）大鼠的体重、总脂肪量（均高达两倍，两者p < 0.001）显著高于瘦对照组和非诺贝特治疗组，空腹血浆胰岛素、瘦素和甘油三酯水平升高（高达110%；p < 0.001），但血糖或非酯化脂肪酸（NEFA）水平无差异。三组肠系膜阻力动脉对氯化钾和去甲肾上腺素诱导的血管收缩反应相似。然而，与瘦对照组相比，未治疗和非诺贝特治疗的饮食喂养组的内皮依赖性血管舒张反应均向右偏移。非诺贝特治疗仅在高浓度卡巴胆碱（10 microM）时改善内皮依赖性血管舒张。三组之间的非内皮依赖性血管舒张无差异。这些结果表明，在存在致肥胖饮食的情况下，非诺贝特显著逆转肥胖并纠正胰岛素抵抗和脂质水平，但对血管功能仅具有有限的有益作用。因此，似乎饮食成分而非肥胖本身在血管异常的发生中起关键作用。
