Neurophysiology Unit, Faculty of Medicine, Cardiac Electrophysiology Research and Training Center, Chiang Mai University, Chiang Mai, Thailand.
Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Menopause. 2018 Dec;25(12):1448-1458. doi: 10.1097/GME.0000000000001149.
Previous studies have demonstrated that either an obese-insulin resistance condition or a condition involving loss of estrogen impaired skeletal muscle function as indicated by a decrease in muscle contraction. The differing effects of combined estrogen deficiency over obese-insulin resistance on skeletal muscle function have, however, not yet been determined. Our hypothesis was that estrogen deficiency aggravates skeletal muscle dysfunction in obese-insulin resistant rats, via increased muscle oxidative stress and mitochondrial dysfunction.
Twenty-four female Wistar rats were divided into 2 groups and animals in each group were fed either a normal diet (ND) or a high-fat diet (HFD) for 24 weeks. At week 13, rats in each group were subdivided into 2 subgroups: sham-operated or ovariectomized (n = 6/subgroup). At the end of the experimental period the contraction of the gastrocnemius muscles was tested before the rats were sacrificed. Skeletal muscle was removed to assess oxidative stress and mitochondrial function.
We found that an obese-insulin resistant condition was observed in sham-operated HFD-fed rats, ovariectomized ND-fed rats, and ovariectomized HFD-fed rats. Skeletal muscle contractile function (peak-force ratio [g/g]; 25.40 ± 2.03 [ovariectomized ND-fed rats], 22.44 ± 0.85 [sham-operated HFD-fed rats] and 25.06 ± 0.61 [ovariectomized HFD-fed rats]), skeletal muscle mitochondrial function, and oxidative stress were equally significantly impaired in all 3 groups, when compared with those of sham-operated ND-fed rats (31.12 ± 1.88 g/g [NDS]; P < 0.05). Surprisingly, loss of estrogen did not aggravate these dysfunctions of skeletal muscles in HFD-fed rats.
These findings suggest that skeletal muscle dysfunction may occur due to increased muscle oxidative stress and mitochondrial dysfunction as a result of ovariectomy and obese-insulin resistance. Loss of estrogen, however, did not aggravate these impairments in the muscle of rats with obese-insulin resistant condition.
先前的研究表明，肥胖伴胰岛素抵抗或雌激素缺乏的状态均可导致骨骼肌功能下降，表现为肌肉收缩力减弱。然而，联合雌激素缺乏与肥胖伴胰岛素抵抗对骨骼肌功能的不同影响尚未确定。我们的假设是，雌激素缺乏通过增加肌肉氧化应激和线粒体功能障碍加重肥胖伴胰岛素抵抗大鼠的骨骼肌功能障碍。
将 24 只雌性 Wistar 大鼠分为 2 组，每组动物分别给予正常饮食（ND）或高脂肪饮食（HFD）24 周。在第 13 周时，每组动物再分为 2 个亚组：假手术或卵巢切除术（n = 6/亚组）。实验期末，在处死大鼠前测试腓肠肌的收缩。取出骨骼肌以评估氧化应激和线粒体功能。
我们发现，假手术 HFD 喂养大鼠、卵巢切除 ND 喂养大鼠和卵巢切除 HFD 喂养大鼠均存在肥胖伴胰岛素抵抗状态。与假手术 ND 喂养大鼠（25.40 ± 2.03 [卵巢切除 ND 喂养大鼠]、22.44 ± 0.85 [假手术 HFD 喂养大鼠]和 25.06 ± 0.61 [卵巢切除 HFD 喂养大鼠]）相比，骨骼肌收缩功能（峰值力比[g/g]）、骨骼肌线粒体功能和氧化应激在所有 3 组中均同样显著受损（P < 0.05）。令人惊讶的是，在 HFD 喂养大鼠中，雌激素缺失并未加重这些骨骼肌功能障碍。
这些发现表明，由于卵巢切除术和肥胖伴胰岛素抵抗导致的肌肉氧化应激和线粒体功能障碍可能导致骨骼肌功能障碍。然而，雌激素缺失并未加重肥胖伴胰岛素抵抗大鼠肌肉的这些损伤。
