Nthlane Refentshe Amandu's, Scheuermaier Karine, Mkhize Siluleko Advice, Michel Frédéric Sébastien
Wits Integrated Molecular Physiology Research Initiative, Wits Health Consortium (PTY) Ltd, School of Biomedical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Wits Sleep Laboratory, Brain Function Research Group, School of Biomedical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
J Biol Rhythms. 2025 Aug;40(4):384-399. doi: 10.1177/07487304251347464. Epub 2025 Jun 19.
Postmenopausal shift workers face increased cardiometabolic risk due to estrogen decline and shift work-induced circadian misalignment. Yet, their combined effects remain poorly understood, especially in hypertensive individuals. This study investigated whether circadian misalignment worsens cardiometabolic parameters in a hypertensive ovariectomized rat model. Female spontaneously hypertensive rats (SHR) were ovariectomized or sham-operated (7-week-old), and then exposed to a chronic phase shift (CPS) protocol or a control light schedule for 10 weeks ( = 9 per group). Measurements included body mass, food and water intake, blood pressure (BP), fasting glucose, glucose tolerance, organ masses, and low-density lipoprotein (LDL) concentration. Ovariectomized rats were heavier and had greater food intake and organ masses than sham-operated rats. However, food intake and organ masses were reduced relative to body mass. CPS rats had greater water intake and reduced liver mass than control light rats. In addition, ovariectomized rats showed lower glucose concentration than sham-operated rats, whereas CPS rats showed higher glucose concentration than control light rats during the oral glucose tolerance test. Moreover, the CPS rats had higher systolic BP. The LDL and fasting glucose concentrations were similar. No interaction between ovariectomy and CPS was observed. These findings suggest that estrogen deficiency increases body mass, but does not worsen cardiometabolic parameters in female SHR. CPS-induced circadian misalignment altered water intake, liver mass, systolic BP and glucose tolerance in the CPS condition in female SHR. This study was unable to monitor physiological or behavioral indicators to confirm circadian misalignment by the CPS protocol. However, the findings provide novel insights into how CPSs independently impair cardiometabolic outcomes in female SHR, with implications for understanding risk in postmenopausal shift workers.
绝经后轮班工作者由于雌激素水平下降和轮班工作导致的昼夜节律失调,面临着更高的心脏代谢风险。然而,它们的综合影响仍知之甚少,尤其是在高血压个体中。本研究调查了昼夜节律失调是否会使高血压去卵巢大鼠模型的心脏代谢参数恶化。将雌性自发性高血压大鼠(SHR)在7周龄时进行去卵巢手术或假手术,然后暴露于慢性相位偏移(CPS)方案或对照光照时间表下10周(每组n = 9)。测量指标包括体重、食物和水摄入量、血压(BP)、空腹血糖、葡萄糖耐量、器官质量和低密度脂蛋白(LDL)浓度。去卵巢大鼠比假手术大鼠体重更重,食物摄入量和器官质量更大。然而,相对于体重,食物摄入量和器官质量有所降低。CPS大鼠比对照光照大鼠水摄入量更大,肝脏质量更小。此外,在口服葡萄糖耐量试验中,去卵巢大鼠的葡萄糖浓度低于假手术大鼠,而CPS大鼠的葡萄糖浓度高于对照光照大鼠。此外,CPS大鼠的收缩压更高。LDL和空腹葡萄糖浓度相似。未观察到去卵巢和CPS之间的相互作用。这些发现表明,雌激素缺乏会增加体重,但不会使雌性SHR的心脏代谢参数恶化。CPS诱导的昼夜节律失调改变了雌性SHR在CPS条件下的水摄入量、肝脏质量、收缩压和葡萄糖耐量。本研究无法通过CPS方案监测生理或行为指标来确认昼夜节律失调。然而这些发现为CPS如何独立损害雌性SHR的心脏代谢结果提供了新的见解,对理解绝经后轮班工作者的风险具有重要意义。