a Nutrition and Exercise Physiology , University of Missouri , Columbia , MO , United States.
b Biomedical Sciences , University of Missouri , Columbia , MO , United States.
Adipocyte. 2018 Jan 2;7(1):35-44. doi: 10.1080/21623945.2017.1405191. Epub 2017 Dec 28.
In rodents, experimentally-induced ovarian hormone deficiency increases adiposity and adipose tissue (AT) inflammation, which is thought to contribute to insulin resistance and increased cardiovascular disease risk. However, whether this occurs in a translationally-relevant large animal model remains unknown. Herein, we tested the hypothesis that ovariectomy would promote visceral and perivascular AT (PVAT) inflammation, as well as subsequent insulin resistance and peripheral vascular dysfunction in female swine. At sexual maturity (7 months of age), female Yucatan mini-swine either remained intact (control, n = 9) or were ovariectomized (OVX, n = 7). All pigs were fed standard chow (15-20 g/kg), and were euthanized 6 months post-surgery. Uterine mass and plasma estradiol levels were decreased by ∼10-fold and 2-fold, respectively, in OVX compared to control pigs. Body mass, glucose homeostasis, and markers of insulin resistance were not different between control and OVX pigs; however, OVX animals exhibited greater plasma triglycerides and triglyceride:HDL ratio. Ovariectomy enhanced visceral adipocyte expansion, although this was not accompanied by brachial artery PVAT adipocyte expansion, AT inflammation in either depot, or increased systemic inflammation assessed by plasma C-reactive protein concentrations. Despite the lack of AT inflammation and insulin resistance, OVX pigs exhibited depressed brachial artery endothelial-dependent vasorelaxation, which was rescued with blockade of endothelin receptor A. Together, these findings indicate that in female Yucatan mini-swine, increased AT inflammation and insulin resistance are not required for loss of ovarian hormones to induce endothelial dysfunction.
在啮齿动物中，实验性诱导的卵巢激素缺乏会增加肥胖和脂肪组织 (AT) 炎症，这被认为是导致胰岛素抵抗和增加心血管疾病风险的原因。然而，这种情况是否会在具有转化相关性的大型动物模型中发生尚不清楚。在此，我们检验了这样一个假设，即卵巢切除术会促进雌性猪的内脏和血管周围 AT (PVAT) 炎症，以及随后的胰岛素抵抗和外周血管功能障碍。在性成熟（7 个月大）时，雌性尤卡坦迷你猪要么保持完整（对照组，n = 9），要么接受卵巢切除术（OVX 组，n = 7）。所有猪都喂食标准饲料（15-20 克/公斤），并在手术后 6 个月处死。与对照组相比，OVX 组的子宫质量和血浆雌二醇水平分别降低了约 10 倍和 2 倍。OVX 组与对照组的体重、葡萄糖稳态和胰岛素抵抗标志物没有差异；然而，OVX 动物的血浆甘油三酯和甘油三酯：HDL 比值更高。卵巢切除术增强了内脏脂肪细胞的扩张，尽管这并没有伴随着肱动脉 PVAT 脂肪细胞的扩张、任何一个脂肪库的 AT 炎症或通过血浆 C 反应蛋白浓度评估的全身炎症增加。尽管没有 AT 炎症和胰岛素抵抗，OVX 猪表现出肱动脉内皮依赖性血管舒张功能受损，这可以通过阻断内皮素受体 A 来挽救。总之，这些发现表明，在雌性尤卡坦迷你猪中，增加的 AT 炎症和胰岛素抵抗不是卵巢激素丧失导致内皮功能障碍所必需的。
