Kocher Caitlin, Christiansen Matthew, Martin Sarah, Adams Christopher, Wehner Paulette, Gress Todd, Santanam Nalini
Department of Pharmacology, Physiology, & Toxicology, Joan C Edwards School of Medicine, Marshall University, One John Marshall Dr, Huntington, WV, 25755, USA.
Department of Medicine and Cardiology, Joan C Edwards School of Medicine, Marshall University, One John Marshall Dr, Huntington, WV, 25755, USA.
J Physiol Biochem. 2017 May;73(2):215-224. doi: 10.1007/s13105-016-0542-0. Epub 2016 Dec 24.
Aging increases the risk of cardiovascular disease and metabolic syndrome. Alterations in epicardial fat play an important pathophysiological role in coronary artery disease and hypertension. We investigated the impact of normal aging on obesity-related genes in epicardial fat. Sex-specific changes in obesity-related genes with aging in epicardial fat (EF) were determined in young (6 months) and old (30/36 months) female and male, Fischer 344 × Brown Norway hybrid (FBN) rats, using a rat obesity RT PCR Array. Circulating sex hormone levels, body and heart weights were determined. Statistical significance was determined using two-tailed Student's t test and Pearson's correlation. Our results revealed sex-specific differences in obesity-related genes with aging. Dramatic changes in the expression profile of obesity-related genes in EF with aging in female, but not in male, FBN rats were observed. The older (30 months) female rats had more significant variations in the abundance of obesity-related genes in the EF compared to that seen in younger female rats or both age groups in male rats. A correlation of changes in obesity-related genes in EF to heart weights was observed in female rats, but not in male rats with aging. No correlation was observed to circulating sex hormone levels. Our findings indicate a dysfunctional EF in female rats with aging compared to male rats. These findings, with further functional validation, might help explain the sex differences in cardiovascular risk and mortality associated with aging observed in humans.
衰老会增加心血管疾病和代谢综合征的风险。心外膜脂肪的改变在冠状动脉疾病和高血压中起着重要的病理生理作用。我们研究了正常衰老对心外膜脂肪中肥胖相关基因的影响。使用大鼠肥胖RT PCR阵列,在年轻(6个月)和年老(30/36个月)的雌性和雄性Fischer 344×Brown Norway杂交(FBN)大鼠中,确定了心外膜脂肪(EF)中肥胖相关基因随衰老的性别特异性变化。测定了循环性激素水平、体重和心脏重量。使用双尾学生t检验和皮尔逊相关性确定统计学意义。我们的结果揭示了肥胖相关基因随衰老的性别特异性差异。在雌性FBN大鼠中观察到EF中肥胖相关基因的表达谱随衰老发生显著变化,而在雄性大鼠中未观察到。与年轻雌性大鼠或两个年龄组的雄性大鼠相比,30个月大的雌性大鼠的心外膜脂肪中肥胖相关基因的丰度有更显著的变化。在雌性大鼠中观察到EF中肥胖相关基因的变化与心脏重量相关,但在衰老的雄性大鼠中未观察到。未观察到与循环性激素水平的相关性。我们的研究结果表明,与雄性大鼠相比,衰老雌性大鼠的心外膜脂肪功能失调。这些发现经过进一步的功能验证,可能有助于解释在人类中观察到的与衰老相关的心血管风险和死亡率的性别差异。