Milutinović Danijela Vojnović, Nikolić Marina, Veličković Nataša, Djordjevic Ana, Bursać Biljana, Nestorov Jelena, Teofilović Ana, Antić Ivana Božić, Macut Jelica Bjekić, Zidane Abdulbaset Shirif, Matić Gordana, Macut Djuro
Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Exp Clin Endocrinol Diabetes. 2017 Sep;125(8):522-529. doi: 10.1055/s-0043-104531. Epub 2017 Apr 13.
Polycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder associated with abdominal obesity, dyslipidemia and insulin resistance. Since abdominal obesity is characterized by low-grade inflammation, the aim of the study was to investigate whether visceral adipose tissue inflammation linked to abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in the animal model of polycystic ovary syndrome.Female Wistar rats were treated with nonaromatizable 5α-dihydrotestosterone pellets in order to induce reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose, triglycerides, non-esterified fatty acids and insulin were determined in blood plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor kappa B intracellular distribution, macrophage migration inhibitory factor protein level, as well as TNFα, IL6 and IL1β mRNA levels. Insulin sensitivity was assessed by intraperitoneal glucose tolerance test and homeostasis model assessment index, and through analysis of insulin signaling pathway in the visceral adipose tissue.Dihydrotestosterone treatment led to increased body weight, abdominal obesity and elevated triglycerides and non-esterified fatty acids, which were accompanied by the activation of nuclear factor kappa B and increase in macrophage migration inhibitory factor, IL6 and IL1β levels in the visceral adipose tissue. In parallel, insulin sensitivity was affected in 5α-dihydrotestosterone-treated animals only at the systemic and not at the level of visceral adipose tissue.The results showed that abdominal obesity and dyslipidemia in the animal model of polycystic ovary syndrome were accompanied with low-grade inflammation in the visceral adipose tissue. However, these metabolic disturbances did not result in decreased tissue insulin sensitivity.
多囊卵巢综合征是一种异质性的内分泌和代谢紊乱疾病，与腹部肥胖、血脂异常和胰岛素抵抗有关。由于腹部肥胖的特征是低度炎症，本研究的目的是调查在多囊卵巢综合征动物模型中，与腹部肥胖和血脂异常相关的内脏脂肪组织炎症是否会导致胰岛素敏感性受损。雌性Wistar大鼠接受不可芳香化的5α-双氢睾酮植入物治疗，以诱导多囊卵巢综合征的生殖和代谢特征。测定血浆中的葡萄糖、甘油三酯、非酯化脂肪酸和胰岛素。通过核因子κB的细胞内分布、巨噬细胞迁移抑制因子蛋白水平以及TNFα、IL6和IL1β mRNA水平评估内脏脂肪组织炎症。通过腹腔葡萄糖耐量试验和稳态模型评估指数，并通过分析内脏脂肪组织中的胰岛素信号通路来评估胰岛素敏感性。双氢睾酮治疗导致体重增加、腹部肥胖以及甘油三酯和非酯化脂肪酸升高，同时伴有核因子κB的激活以及内脏脂肪组织中巨噬细胞迁移抑制因子、IL6和IL1β水平的增加。与此同时，胰岛素敏感性仅在全身水平受到影响，而在内脏脂肪组织水平未受影响。结果表明，多囊卵巢综合征动物模型中的腹部肥胖和血脂异常伴有内脏脂肪组织的低度炎症。然而，这些代谢紊乱并未导致组织胰岛素敏感性降低。
