Heras-Molina Ana, Pesantez-Pacheco José Luis, Vazquez-Gomez Marta, Garcia-Contreras Consolacion, Astiz Susana, Isabel Beatriz, Gonzalez-Bulnes Antonio
Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Ctra. De La Coruña Km. 7,5., 28040 Madrid, Spain.
School of Veterinary Medicine and Zootechnics, Faculty of Agricultural Sciences, University of Cuenca, Avda. Doce de Octubre, Cuenca 010220, Ecuador.
Biology (Basel). 2020 Sep 11;9(9):284. doi: 10.3390/biology9090284.
Menopause strongly increases incidence and consequences of obesity and non-communicable diseases in women, with recent research suggesting a very early onset of changes in lipid accumulation, dyslipidemia, and insulin resistance. However, there is a lack of adequate preclinical models for its study. The present trial evaluated the usefulness of an alternative method to surgical ovariectomy, the administration of two doses of a GnRH analogue-protein conjugate (Vacsincel), for inducing ovarian inactivity in sows used as preclinical models of obesity and menopause. All the sows treated with the compound developed ovarian stoppage after the second dose and, when exposed to obesogenic diets during the following three months, showed changes in the patterns of fat deposition, in the fatty acids profiles at the different tissues and in the plasma concentrations of fructosamine, urea, β-hydroxibutirate, and haptoglobin when compared to obese fed with the same diet but maintaining ovarian activity. Altogether, these results indicate that menopause early augments the deleterious effects induced by overfeeding and obesity on metabolic traits, paving the way for future research on physiopathology of these conditions and possible therapeutic targets using the swine model.
绝经会显著增加女性肥胖和非传染性疾病的发病率及后果,近期研究表明脂质蓄积、血脂异常和胰岛素抵抗的变化在绝经初期就已出现。然而,目前缺乏用于研究绝经的合适临床前模型。本试验评估了一种替代手术去卵巢的方法的有效性,即给予两剂促性腺激素释放激素类似物-蛋白质缀合物(Vacsincel),以诱导母猪卵巢功能减退,该母猪用作肥胖和绝经的临床前模型。所有接受该化合物治疗的母猪在第二次给药后均出现卵巢停止活动,并且在接下来的三个月中,当与食用相同饮食但保持卵巢活动的肥胖母猪相比,在接受致肥饮食时,它们在脂肪沉积模式、不同组织中的脂肪酸谱以及血浆中果糖胺、尿素、β-羟基丁酸酯和触珠蛋白的浓度方面均出现了变化。总之,这些结果表明绝经会早期增强过量进食和肥胖对代谢特征的有害影响,为未来利用猪模型研究这些病症的病理生理学和可能的治疗靶点铺平了道路。