Tikellis Christos, Thomas Merlin C, Harcourt Brooke E, Coughlan Melinda T, Pete Josepha, Bialkowski Katarzyna, Tan Adeline, Bierhaus Angelika, Cooper Mark E, Forbes Josephine M
Baker Medical Research Institute, Melbourne, Victoria 8008, Australia.
Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E323-30. doi: 10.1152/ajpendo.00024.2008. Epub 2008 May 13.
A diet high in fat induces cardiac hypertrophy, inflammation, and oxidative stress. Although such actions have largely been ascribed to fat deposition, the accumulation of advanced glycation end products (AGEs) and subsequent activation of the receptor for AGEs (RAGE) may also represent important mediators of cardiac injury following exposure to a Western diet. In this study, male C57BL6J and RAGE knockout mice were placed on either a standard diet (7% fat) or a Western "fast-food" diet (21% fat). Animals receiving a high-fat diet were further randomized to receive the AGE inhibitor alagebrium chloride (1 mg.kg(-1).day(-1)) and followed for 16 wk. A Western diet was associated with cardiac hypertrophy, inflammation, mitochondrial-dependent superoxide production, and cardiac AGE accumulation in wild-type mice. Although RAGE-KO mice fed a Western diet also became obese and accumulated intramyocardial lipid, cardiomyocyte hypertrophy, inflammation, and oxidative stress were attenuated compared with wild-type mice. Similarly, mice of both strains receiving alagebrium chloride had reduced levels of inflammation and oxidative stress, in association with a reduction in cardiac AGEs and RAGE. This study suggests that AGEs represent important mediators of cardiac injury associated with a Western fast-food diet. These data point to the potential utility of AGE-reducing strategies in the prevention and management of cardiac disease.
高脂肪饮食会诱发心脏肥大、炎症和氧化应激。尽管这些作用很大程度上归因于脂肪沉积，但晚期糖基化终产物（AGEs）的积累以及随后的AGE受体（RAGE）激活，也可能是西方饮食导致心脏损伤的重要介质。在本研究中，将雄性C57BL6J和RAGE基因敲除小鼠分别置于标准饮食（7%脂肪）或西方“快餐”饮食（21%脂肪）中。接受高脂肪饮食的动物进一步随机分组，接受AGE抑制剂氯化阿糖腺苷（1 mg·kg⁻¹·d⁻¹），并持续观察16周。西方饮食与野生型小鼠的心脏肥大、炎症、线粒体依赖性超氧化物产生以及心脏AGE积累有关。尽管喂食西方饮食的RAGE基因敲除小鼠也变得肥胖并积累了心肌内脂质，但与野生型小鼠相比，心肌细胞肥大、炎症和氧化应激有所减轻。同样，两种品系接受氯化阿糖腺苷的小鼠炎症和氧化应激水平均降低，同时心脏AGEs和RAGE减少。本研究表明，AGEs是与西方快餐饮食相关的心脏损伤的重要介质。这些数据表明降低AGEs的策略在预防和管理心脏病方面具有潜在效用。
