Laboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Department of Surgery, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Exp Cell Res. 2019 Apr 15;377(1-2):47-55. doi: 10.1016/j.yexcr.2019.02.015. Epub 2019 Feb 19.
Brown and beige adipocytes contribute significantly to the regulation of whole body energy expenditure and systemic metabolic homeostasis not exclusively by thermogenesis through mitochondrial uncoupling. Several studies have provided evidence in rodents that brown and beige adipocytes produce a set of adipokines ("batokines") which regulate local tissue homeostasis and have beneficial effects on physiological functions of the entire body. We observed elevated secretion of Interleukin (IL)-6, IL-8 and monocyte chemoattractant protein (MCP)-1, but not tumor necrosis factor alpha (TNFα) or IL-1β pro-inflammatory cytokines, by ex vivo differentiating human beige adipocytes (induced by either PPARγ agonist or irisin) compared to white. Higher levels of IL-6, IL-8 and MCP-1 were released from human deep neck adipose tissue biopsies (enriched in browning cells) than from subcutaneous ones. IL-6 was produced in a sustained manner and mostly by the adipocytes and not by the undifferentiated progenitors. Continuous blocking of IL-6 receptor by specific antibody during beige differentiation resulted in downregulation of brown marker genes and increased morphological changes that are characteristic of white adipocytes. The data suggest that beige adipocytes adjust their production of IL-6 to reach an optimal level for differentiation in the medium enhancing browning in an autocrine manner.
棕色和米色脂肪细胞通过解耦联作用产生热量来调节全身能量消耗和系统代谢平衡,这一作用并非其唯一贡献。多项研究表明,棕色和米色脂肪细胞会产生一组调节局部组织稳态的脂肪因子(“BATOKINES”),从而对全身的生理功能产生有益影响。我们发现,与白色脂肪细胞相比,体外分化的人类米色脂肪细胞(由过氧化物酶体增殖物激活受体 γ 激动剂或鸢尾素诱导)会分泌更高水平的白细胞介素 (IL)-6、IL-8 和单核细胞趋化蛋白 1(MCP-1),但不分泌肿瘤坏死因子-α(TNFα)或白细胞介素-1β 等促炎细胞因子。来自人类深颈部脂肪组织活检的样本(富含棕色细胞)释放的 IL-6、IL-8 和 MCP-1 水平高于来自皮下组织的样本。IL-6 以持续的方式产生,主要来自脂肪细胞,而不是未分化的祖细胞。在米色分化过程中,通过特异性抗体持续阻断 IL-6 受体,会导致棕色标记基因的下调和白色脂肪细胞特有的形态变化增加。数据表明,米色脂肪细胞会调整其 IL-6 的产生,以达到促进自身分化的最佳水平,从而增强棕色化。