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; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand.
Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand.
Exp Gerontol. 2018 Mar;103:107-114. doi: 10.1016/j.exger.2018.01.006. Epub 2018 Jan 10.
The incidence of cardiovascular disease and metabolic syndrome increases after the onset of menopause, suggesting estrogen has a vital role in their prevention. Mitochondrial dynamics are known to play an important role in the maintenance of cardiac physiological function. However, the effects of estrogen deprivation on cardiometabolic status and cardiac mitochondrial dynamics under conditions of obese-insulin resistance have never been investigated. We hypothesized that estrogen deprivation aggravates cardiac dysfunction through increased cardiac mitochondrial fission in obese-insulin resistant rats. Female rats were fed on either a high fat (HFD, 57.60% fat) or normal (ND, 19.77% fat) diet for 13 weeks. The rats were then divided into 4 groups. Two sham groups (HFS and NDS) and 2 operated or ovariectomized (HFO and NDO) groups (n = 8/group). Six weeks after surgery, metabolic status, heart rate variability (HRV), left ventricular (LV) function, cardiac mitochondrial function and dynamics, and metabolic parameters were determined. Insulin resistance developed in NDO, HFS and HFO rats as indicated by increased plasma insulin and HOMA index. Although rats in both NDO and HFS groups had markedly impaired LV function indicated by reduced %LVFS and impaired cardiac mitochondrial function, rats in the HFO group had the most severe impairments. Moreover, the estrogen deprived rats (NDO and HFO) had increased cardiac mitochondrial fission through activation of phosphorylation of Drp-1 at serine 616. Our findings indicated that estrogen deprivation caused the worsening of LV dysfunction through increased cardiac mitochondrial fission in obese-insulin resistant rats.
绝经后心血管疾病和代谢综合征的发病率增加，这表明雌激素在预防这些疾病中起着至关重要的作用。线粒体动力学在维持心脏生理功能方面起着重要作用。然而，在肥胖-胰岛素抵抗的情况下，雌激素缺乏对心脏代谢状态和心脏线粒体动力学的影响从未被研究过。我们假设，在肥胖-胰岛素抵抗的大鼠中，雌激素缺乏通过增加心脏线粒体裂变加剧心脏功能障碍。雌性大鼠接受高脂（HFD，57.60%脂肪）或正常饮食（ND，19.77%脂肪）喂养 13 周。然后将大鼠分为 4 组。2 个假手术组（HFS 和 NDS）和 2 个手术或卵巢切除组（HFO 和 NDO）（每组 n=8）。手术后 6 周，测定代谢状态、心率变异性（HRV）、左心室（LV）功能、心脏线粒体功能和动力学以及代谢参数。NDO、HFS 和 HFO 大鼠的胰岛素抵抗表现为血浆胰岛素和 HOMA 指数增加。尽管 NDO 和 HFS 组大鼠的 LV 功能明显受损，表现为%LVFS 降低和心脏线粒体功能受损，但 HFO 组大鼠的损伤最严重。此外，雌激素剥夺的大鼠（NDO 和 HFO）通过激活 Drp-1 丝氨酸 616 的磷酸化导致心脏线粒体裂变增加。我们的研究结果表明，在肥胖-胰岛素抵抗的大鼠中，雌激素缺乏通过增加心脏线粒体裂变导致 LV 功能障碍恶化。
