Abstract:
Circadian disruption increases the development of cardiovascular disease and diabetes. We found that circadian disruption causes glucose intolerance, cardiac fibrosis and adipocyte tissue dysfunction in male sand rats, Psammomys obesus. Whether these effects occur in female P. obesus is unknown. Male and female P. obesus were fed a high energy diet and exposed to a neutral (12 light:12 dark, control) or short (5 light:19 dark, circadian disruption) photoperiod for 20 weeks. Circadian disruption impaired glucose tolerance in males but not females. It also increased cardiac perivascular fibrosis and cardiac expression of inflammatory marker Ccl2 in males, with no effect in females. Females had reduced proapoptotic Bax mRNA and cardiac Myh7:Myh6 hypertrophy ratio. Cardiac protection in females occurred despite reductions in the clock gene Per2. Circadian disruption increased adipocyte hypertrophy in both males and females. This was concomitant with a reduction in adipocyte differentiation markers Pparg and Cebpa in males and females, respectively. Circadian disruption increased visceral adipose expression of inflammatory mediators Ccl2, Tgfb1 and Cd68 and reduced browning marker Ucp1 in males. However, these changes were not observed in females. Collectively, our study show that sex differentially influences the effects of circadian disruption on glucose tolerance, cardiac function and adipose tissue dysfunction.
摘要:
昼夜节律中断会增加心血管疾病和糖尿病的发展。我们发现昼夜节律中断会导致葡萄糖不耐受,雄性沙鼠心肌纤维化和脂肪细胞组织功能障碍,Psammomysobesus.这些影响是否发生在女性肥胖假单胞菌中是未知的。雄性和雌性奥贝斯接受高能量饮食,并暴露于中性饮食(12光照:12黑暗,控制)或短(5光:19暗,昼夜节律中断)光周期为20周。昼夜节律中断会损害男性而非女性的葡萄糖耐量。它还增加了男性的心脏血管周围纤维化和心脏炎症标志物Ccl2的表达,对女性没有影响。女性的促凋亡BaxmRNA和心脏Myh7:Myh6肥大比率降低。尽管时钟基因Per2减少,但女性仍存在心脏保护。昼夜节律破坏增加了男性和女性的脂肪细胞肥大。这伴随着男性和女性脂肪细胞分化标志物Pparg和Cebpa的减少,分别。昼夜节律破坏增加了男性炎症介质Ccl2,Tgfb1和Cd68的内脏脂肪表达,并降低了褐变标记Ucp1。然而,这些变化在女性中未观察到。总的来说,我们的研究表明,性别差异影响昼夜节律中断对糖耐量的影响,心功能和脂肪组织功能障碍。