School of Medicine, The University of Nottingham, UK; Faculty of Biology, The University of Belgrade, Serbia.
School of Medicine, The University of Nottingham, UK.
Eur J Cell Biol. 2023 Sep;102(3):151342. doi: 10.1016/j.ejcb.2023.151342. Epub 2023 Jul 13.
Although phenotypically different, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) are able to produce heat through non-shivering thermogenesis due to the presence of mitochondrial uncoupling protein 1 (UCP1). The appearance of thermogenically active beige adipocytes in iWAT is known as browning. Both brown and beige cells originate from mesenchymal stem cells (MSCs), and in culture conditions a browning response can be induced with hypothermia (i.e. 32 °C) during which nuclear leptin immunodetection was observed. The central role of leptin in regulating food intake and energy consumption is well recognised, but its importance in the browning process at the cellular level is unclear. Here, immunocytochemical analysis of MSC-derived adipocytes established nuclear localization of both leptin and leptin receptor suggesting an involvement of the leptin pathway in the browning response. In order to elucidate whether leptin modulates the expression of brown and beige adipocyte markers, BAT and iWAT samples from leptin-deficient (ob/ob) mice were analysed and exhibited reduced brown/beige marker expression compared to wild-type controls. When MSCs were isolated and differentiated into adipocytes, leptin deficiency was observed to induce a white phenotype, especially when incubated at 32 °C. These adaptations were accompanied with morphological signs of impaired adipogenic differentiation. Overall, our results indicate that leptin supports adipocyte browning and suggest a potential role for leptin in adipogenesis and browning.
虽然表型不同，但棕色脂肪组织 (BAT) 和腹股沟白色脂肪组织 (iWAT) 由于存在线粒体解偶联蛋白 1 (UCP1)，能够通过非颤抖产热产生热量。iWAT 中出现的具有产热活性的米色脂肪细胞称为褐变。棕色和米色细胞均源自间充质干细胞 (MSC)，在低温 (即 32°C) 培养条件下可以诱导褐变反应，在此期间观察到核瘦素免疫检测。瘦素在调节食物摄入和能量消耗方面的核心作用是众所周知的，但它在细胞水平上对褐变过程的重要性尚不清楚。在这里，对 MSC 衍生的脂肪细胞进行免疫细胞化学分析表明，瘦素和瘦素受体均定位于核内，表明瘦素途径参与了褐变反应。为了阐明瘦素是否调节棕色和米色脂肪细胞标志物的表达，分析了瘦素缺乏型 (ob/ob) 小鼠的 BAT 和 iWAT 样本，与野生型对照相比，其棕色/米色标志物表达减少。当分离 MSC 并分化为脂肪细胞时，观察到瘦素缺乏会诱导白色表型，尤其是在 32°C 下孵育时。这些适应伴随着脂肪生成分化受损的形态学迹象。总的来说，我们的结果表明瘦素支持脂肪细胞褐变，并表明瘦素在脂肪生成和褐变中可能具有潜在作用。
