Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Geroscience. 2020 Feb;42(1):233-249. doi: 10.1007/s11357-019-00132-9. Epub 2019 Nov 25.
The prevalence of obesity and an aging population are increasing worldwide. Both obesity and aging are independently known to be associated with cardiac dysfunction. However, in obese insulin-resistant subjects, the effects of aging on metabolic status and cardiac and mitochondrial functions are not completely understood. We hypothesized that in the obese insulin-resistant condition, aging induced by D-galactose increases cardiac senescence markers and aggravates the impairment of metabolic parameters, cardiac and mitochondrial function, and increases oxidative stress, inflammation, apoptosis, and autophagy. Sixty-four male Wistar rats were fed with either normal diet (ND) or high-fat diet (HFD) for 12 weeks. Then, rats were divided into vehicle groups (0.9% NSS, subcutaneous injection (SC)) or D-galactose groups (150 mg/kg/day, SC). After 0.9%NSS or D-galactose treatment for 4 weeks and 8 weeks, metabolic and cardiac functions were determined. The heart was then removed to determine mitochondrial functions and enable biochemical studies. After 4 weeks of D-galactose injection, ND rats treated with D-galactose (NDD4), HFD rats treated with vehicle (HFV4), and HFD rats treated with D-galactose (HFD4) had reduced cardiac function, impaired cardiac mitochondrial function and autophagy, and increased oxidative stress, inflammation, and apoptosis. Interestingly, after 8 weeks, HFD rats treated with D-galactose (HFD8) had the worst impairment of cardiac and mitochondrial function, autophagy, and apoptosis in comparison to the other groups. Aging induced by D-galactose aggravated cardiac dysfunction in obese insulin-resistant rats through the worsening of cardiac mitochondrial function, autophagy, and increased apoptosis in a time-dependent manner.
肥胖症和人口老龄化在全球范围内日益普遍。肥胖症和老龄化都被独立地认为与心脏功能障碍有关。然而，在肥胖胰岛素抵抗的受试者中，衰老对代谢状态以及心脏和线粒体功能的影响尚不完全清楚。我们假设，在肥胖胰岛素抵抗的情况下，D-半乳糖诱导的衰老会增加心脏衰老标志物，并加重代谢参数、心脏和线粒体功能的损害，并增加氧化应激、炎症、细胞凋亡和自噬。64 只雄性 Wistar 大鼠分别用正常饮食（ND）或高脂肪饮食（HFD）喂养 12 周。然后，将大鼠分为载体组（0.9%生理盐水，皮下注射（SC））或 D-半乳糖组（150mg/kg/天，SC）。在 0.9%生理盐水或 D-半乳糖处理 4 周和 8 周后，测定代谢和心脏功能。然后取出心脏以确定线粒体功能并进行生化研究。D-半乳糖注射 4 周后，ND 大鼠用 D-半乳糖处理（NDD4），HFD 大鼠用载体处理（HFV4），HFD 大鼠用 D-半乳糖处理（HFD4）的大鼠心脏功能降低，心脏线粒体功能和自噬受损，氧化应激、炎症和细胞凋亡增加。有趣的是，8 周后，与其他组相比，HFD 大鼠用 D-半乳糖处理（HFD8）的心脏和线粒体功能、自噬和细胞凋亡的损伤最严重。D-半乳糖诱导的衰老通过心脏线粒体功能恶化、自噬增加和细胞凋亡增加，以时间依赖的方式加重肥胖胰岛素抵抗大鼠的心脏功能障碍。
