Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Zurich, Zurich, Switzerland.
Children's Research Center, University Children's Hospital, University of Zurich, Zurich, Switzerland.
Adipocyte. 2022 Dec;11(1):315-324. doi: 10.1080/21623945.2022.2075129.
Oncostatin M (OSM) is a member of the glycoprotein 130 cytokine family that is involved in chronic inflammation and increased in adipose tissue under obesity and insulin resistance. OSM was shown to inhibit adipogenesis, suppress browning, and contribute to insulin resistance in cultured white adipocytes. In contrast, OSM may have a metabolically favourable role on adipocytes in mouse models of obesity and insulin resistance. However, a putative role of OSM in modulating lipolysis has not been investigated in detail to date. To address this, cultured white adipocytes of mouse or human origin were exposed to 10 or 100 ng/ml of OSM for various time periods. In murine 3T3-L1 cells, OSM stimulation directly activated hormone-sensitive lipase (HSL) and other players of the lipolytic machinery, and dose-dependently increased free fatty acid and glycerol release. In parallel, OSM attenuated insulin-mediated suppression of lipolysis and induced phosphorylation of serine-residues on the insulin receptor substrate-1 (IRS1) protein. Key experiments were verified in a second murine and a human adipocyte cell line. Inhibiton of extracellular signal-regulated kinase (ERK)-1/2 activation, abolished OSM-mediated HSL phosphorylation and lipolysis. In conclusion, OSM signalling directly promotes lipolysis in white adipocytes in an ERK1/2-dependent manner.
抑瘤素 M (OSM) 是糖蛋白 130 细胞因子家族的成员，参与慢性炎症，在肥胖和胰岛素抵抗情况下脂肪组织中增加。研究表明，OSM 抑制脂肪生成、抑制棕色化、并导致培养的白色脂肪细胞胰岛素抵抗。相比之下，OSM 可能在肥胖和胰岛素抵抗的小鼠模型中对脂肪细胞具有代谢上有利的作用。然而，迄今为止，尚未详细研究 OSM 在调节脂肪分解中的潜在作用。为了解决这个问题，用 10 或 100ng/ml 的 OSM 处理不同时间的来源于小鼠或人类的培养白色脂肪细胞。在鼠 3T3-L1 细胞中，OSM 刺激直接激活激素敏感脂肪酶 (HSL) 和脂肪分解的其他关键酶，并剂量依赖性地增加游离脂肪酸和甘油释放。同时，OSM 减弱了胰岛素对脂肪分解的抑制作用，并诱导胰岛素受体底物-1(IRS1)蛋白丝氨酸残基磷酸化。在第二个小鼠和人类脂肪细胞系中进行了关键实验验证。细胞外信号调节激酶 (ERK)-1/2 激活的抑制作用，消除了 OSM 介导的 HSL 磷酸化和脂肪分解。总之，OSM 信号以 ERK1/2 依赖的方式直接促进白色脂肪细胞的脂肪分解。
