Camer Danielle, Yu Yinghua, Szabo Alexander, Wang Hongqin, Dinh Chi H L, Huang Xu-Feng
Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia.
Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia; ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, NSW, 2234, Australia.
Chem Biol Interact. 2016 Jan 5;243:10-8. doi: 10.1016/j.cbi.2015.11.018. Epub 2015 Nov 27.
Obesity caused by the consumption of a high-fat (HF) diet is a major risk factor for the development of associated complications, such as heart and kidney failure. A semi-synthetic triterpenoid, bardoxolone methyl (BM) was administrated to mice fed a HF diet for 21 weeks to determine if it would prevent the development of obesity-associated cardiac and renal pathophysiologies. Twelve week old male C57BL/6J mice were fed a lab chow (LC), HF (40% fat), or a HF diet supplemented with 10 mg/kg/day BM in drinking water. After 21 weeks, the left ventricles of hearts and cortex of kidneys of mice were collected for analysis. Histological analysis revealed that BM prevented HF diet-induced development of structural changes in the heart and kidneys. BM prevented HF diet-induced decreases in myocyte number in cardiac tissue, although this treatment also elevated cardiac endothelin signalling molecules. In the kidneys, BM administration prevented HF diet-induced renal corpuscle hypertrophy and attenuated endothelin signalling. Furthermore, in both the hearts and kidneys of mice fed a HF diet, BM administration prevented HF diet-induced increases in fat accumulation, macrophage infiltration and tumour necrosis factor alpha (TNFα) gene expression. These findings suggest that BM prevents HF diet-induced developments of cardiac and renal pathophysiologies in mice fed a chronic HF diet by preventing inflammation. Moreover, these results suggest that BM has the potential as a therapeutic for preventing obesity-induced cardiac and renal pathophysiologies.
高脂（HF）饮食导致的肥胖是引发相关并发症（如心力衰竭和肾衰竭）的主要风险因素。给喂食HF饮食21周的小鼠施用一种半合成三萜类化合物——甲基巴多索隆（BM），以确定其是否能预防与肥胖相关的心脏和肾脏病理生理变化的发生。给12周龄的雄性C57BL/6J小鼠喂食实验室常规饲料（LC）、HF（40%脂肪）饲料或在饮水中添加10 mg/kg/天BM的HF饲料。21周后，收集小鼠的心脏左心室和肾脏皮质进行分析。组织学分析显示，BM可预防HF饮食诱导的心脏和肾脏结构变化。BM可预防HF饮食诱导的心脏组织中肌细胞数量减少，尽管这种处理也会提高心脏内皮素信号分子水平。在肾脏中，施用BM可预防HF饮食诱导的肾小体肥大并减弱内皮素信号传导。此外，在喂食HF饮食的小鼠的心脏和肾脏中，施用BM均可预防HF饮食诱导的脂肪堆积增加、巨噬细胞浸润以及肿瘤坏死因子α（TNFα）基因表达增加。这些发现表明，BM通过预防炎症，可防止长期喂食HF饮食的小鼠出现HF饮食诱导的心脏和肾脏病理生理变化。此外，这些结果表明，BM有潜力作为预防肥胖诱导的心脏和肾脏病理生理变化的治疗药物。
