Balazova L, Krskova K, Suski M, Sisovsky V, Hlavacova N, Olszanecki R, Jezova D, Zorad S
Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
Institute for Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
J Physiol Pharmacol. 2016 Aug;67(4):531-541.
Increasing evidence indicates a role of oxytocin in controlling energy metabolism. The aim of his study was to investigate oxytocin effects on obese phenotype in leptin-resistant Zucker fatty rats, focusing on glucose and lipid metabolism. Zucker fatty rats and their lean controls were treated with oxytocin (3.6 μg/100g body weight/day) by osmotic minipumps implanted subcutaneously for 2 weeks. Two-hours intraperitoneal glucose tolerance test was performed in fasting rats. Oxytocin decreased food intake in both phenotypes while body weight gain reduced only in obese animals. In obese rats oxytocin impaired hepatic insulin extraction and enhanced liver triglyceride accumulation. Moreover, in the skeletal muscle of lean rats oxytocin treatment downregulated insulin signal transduction by decreasing of insulin receptor substrate 1 protein level and stimulating of its serine phosphorylation. Concurrently, the gene expression of insulin receptor substrate 1 in the skeletal muscle and adipose tissue was downregulated by oxytocin. In obese rats, oxytocin reduced adipocyte size and normalised mRNA levels of both fatty acid binding protein 4 and fatty acid synthase but attenuated gene expression of glucose transporter 4. The present study in Zucker fatty rats demonstrated ambivalent effects of oxytocin treatment with predominantly negative impact on skeletal muscle insulin pathway in lean animals.
越来越多的证据表明催产素在控制能量代谢中发挥作用。本研究的目的是调查催产素对瘦素抵抗型 Zucker 肥胖大鼠肥胖表型的影响，重点关注葡萄糖和脂质代谢。通过皮下植入渗透微型泵，以 3.6 μg/100g 体重/天的剂量给 Zucker 肥胖大鼠及其瘦对照注射催产素，持续 2 周。对禁食大鼠进行两小时的腹腔内葡萄糖耐量试验。催产素使两种表型的食物摄入量均减少，而体重增加仅在肥胖动物中减少。在肥胖大鼠中，催产素损害肝脏胰岛素摄取并增加肝脏甘油三酯积累。此外，在瘦大鼠的骨骼肌中，催产素处理通过降低胰岛素受体底物 1 蛋白水平并刺激其丝氨酸磷酸化来下调胰岛素信号转导。同时，催产素下调骨骼肌和脂肪组织中胰岛素受体底物 1 的基因表达。在肥胖大鼠中，催产素减小脂肪细胞大小，并使脂肪酸结合蛋白 4 和脂肪酸合酶的 mRNA 水平正常化，但减弱葡萄糖转运蛋白 4 的基因表达。本研究在 Zucker 肥胖大鼠中证明了催产素治疗的矛盾效应，对瘦动物的骨骼肌胰岛素途径主要产生负面影响。
