Institut National de la Santé Et de la Recherche Médicale, U961, Vandoeuvre-les-Nancy, France.
J Gerontol A Biol Sci Med Sci. 2012 Sep;67(9):927-38. doi: 10.1093/gerona/glr236. Epub 2012 Mar 1.
To analyze age-related interactions between obesity, its associated metabolic disorders, and macrocirculation, we studied large artery stiffness and fatty acid responsiveness in lean and obese Zucker rats, aged 25 (adult) and 80 weeks (very old). Systolic arterial pressure was higher in old obese than in old lean rats (178 ± 10 vs 134 ± 8 mmHg, respectively). Carotid elastic modulus-wall stress curves showed increased age-dependent arterial stiffening, which was greater in obese animals. Old obese exhibited endothelial dysfunction with increased systemic oxidative stress. Adult obese had elevated plasma free fatty acid levels (1,866 ± 177 vs 310 ± 34 μg/μL in lean animals). In old obese, linoleate and palmitate increased contractility to phenylephrine and reduced relaxation to acetylcholine. Thus, obesity at 25 weeks appears to trigger accelerated arterial aging observed at 80 weeks. The early increase in free fatty acids may be a key effector in the severe arterial stiffness of the aged obese Zucker model.
为了分析肥胖及其相关代谢紊乱与大循环之间的年龄相关性相互作用，我们研究了瘦型和肥胖型 Zucker 大鼠的大动脉僵硬和脂肪酸反应性，这些大鼠的年龄分别为 25 周（成年）和 80 周（非常老）。老年肥胖大鼠的收缩压高于老年瘦型大鼠（分别为 178 ± 10 与 134 ± 8 mmHg）。颈动脉弹性模量-壁应力曲线显示动脉僵硬随年龄的依赖性增加，肥胖动物的增加更为明显。老年肥胖大鼠表现出内皮功能障碍和全身氧化应激增加。成年肥胖大鼠的血浆游离脂肪酸水平升高（1,866 ± 177 与 310 ± 34 μg/μL，瘦型大鼠）。在老年肥胖大鼠中，亚油酸和棕榈酸增加了对苯肾上腺素的收缩性，减少了对乙酰胆碱的松弛性。因此，25 周时的肥胖似乎引发了 80 周时观察到的加速动脉老化。早期游离脂肪酸的增加可能是老年肥胖 Zucker 模型严重动脉僵硬的关键效应因子。
