Department of Pathology and Immunology, Medical Faculty, University Medical Center, University of Geneva, Geneva, Switzerland.
Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Diabetes Metab. 2018 Jun;44(3):292-295. doi: 10.1016/j.diabet.2017.10.004. Epub 2017 Nov 10.
Oxytocin administration to diet-induced obese (DIO) rodents, monkeys and humans decreases body weight and fat mass with concomitant improvements in glucose metabolism. Moreover, several studies show an immunomodulatory role of oxytocin in a number of settings (such as atherosclerosis, injury, sepsis). This study aims to shed some light on the effects of oxytocin on macrophage polarization and cytokine production, as well as its possible impact on these parameters in adipose tissue in DIO mice with impaired glucose metabolism.
Mouse bone marrow cells were differentiated into macrophages and treated with oxytocin. Macrophage proliferation, cytokine secretion and macrophage populations were determined. For experiments in vivo, DIO mice were treated with oxytocin for 2 weeks. Body weight and composition and glucose tolerance were subsequently followed. At the end of treatment, adipose tissue macrophage populations, plasma cytokine levels and cytokine expression in adipose tissue were determined.
In bone marrow-derived macrophages, oxytocin induced an anti-inflammatory phenotype (decreased M1/M2 ratio). In M1-derived macrophages, oxytocin decreased TNFα secretion, with no effects on the other cytokines tested nor any effect on cytokine secretion by M2-derived macrophages. Oxytocin treatment in DIO mice in vivo led to decreased body weight accompanied by an improvement in glucose tolerance, with no changes in plasma cytokine levels. In adipose tissue, oxytocin decreased Tnfα expression without modifying the M1/M2 macrophage ratio.
Oxytocin treatment decreases TNFα production both in vitro (in bone marrow-derived macrophages) and in vivo (in epididymal adipose tissue) in DIO mice. This effect may also be contributory to the observed improvement in glucose metabolism.
给饮食诱导肥胖（DIO）的啮齿动物、猴子和人类施用催产素可降低体重和脂肪量，同时改善葡萄糖代谢。此外，多项研究表明催产素在多种情况下具有免疫调节作用（如动脉粥样硬化、损伤、败血症）。本研究旨在阐明催产素对巨噬细胞极化和细胞因子产生的影响，以及其对葡萄糖代谢受损的 DIO 小鼠脂肪组织中这些参数的可能影响。
从小鼠骨髓细胞分化而来的巨噬细胞用催产素处理。测定巨噬细胞增殖、细胞因子分泌和巨噬细胞群体。在体内实验中，DIO 小鼠用催产素治疗 2 周。随后监测体重和组成以及葡萄糖耐量。治疗结束时，测定脂肪组织中的巨噬细胞群体、血浆细胞因子水平和脂肪组织中的细胞因子表达。
在骨髓来源的巨噬细胞中，催产素诱导抗炎表型（降低 M1/M2 比值）。在 M1 衍生的巨噬细胞中，催产素降低 TNFα 的分泌，对测试的其他细胞因子没有影响，也对 M2 衍生的巨噬细胞的细胞因子分泌没有影响。在体内的 DIO 小鼠中，催产素治疗导致体重减轻，同时葡萄糖耐量改善，而血浆细胞因子水平没有变化。在脂肪组织中，催产素降低 Tnfα 表达，而不改变 M1/M2 巨噬细胞比值。
催产素治疗可降低 DIO 小鼠体内（在附睾脂肪组织中）和体外（在骨髓来源的巨噬细胞中）TNFα 的产生。这种作用可能有助于观察到的葡萄糖代谢改善。
