Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, Jiangsu, China.
Cell Mol Life Sci. 2023 Nov 27;80(12):377. doi: 10.1007/s00018-023-05027-9.
Although brown adipose tissue (BAT) has historically been viewed as a major site for energy dissipation through thermogenesis, its endocrine function has been increasingly recognized. However, the circulating factors in BAT that play a key role in controlling systemic energy homeostasis remain largely unexplored. Here, we performed a peptidomic analysis to profile the extracellular peptides released from human brown adipocytes upon exposure to thermogenic stimuli. Specifically, we identified a secreted peptide that modulates adipocyte thermogenesis in a cell-autonomous manner, and we named it BATSP1. BATSP1 promoted BAT thermogenesis and induced browning of white adipose tissue in vivo, leading to increased energy expenditure under cold stress. BATSP1 treatment in mice prevented high-fat diet-induced obesity and improved glucose tolerance and insulin resistance. Mechanistically, BATSP1 facilitated the nucleocytoplasmic shuttling of forkhead transcription factor 1 (FOXO1) and released its transcriptional inhibition of uncoupling protein 1 (UCP1). Overall, we provide a comprehensive analysis of the human brown adipocyte extracellular peptidome following acute forskolin (FSK) stimulation and identify BATSP1 as a novel regulator of thermogenesis that may offer a potential approach for obesity treatment.
虽然棕色脂肪组织（BAT）一直被视为通过产热来消耗能量的主要部位，但它的内分泌功能已越来越受到重视。然而，在调节全身能量平衡方面发挥关键作用的 BAT 循环因子在很大程度上仍未得到探索。在这里，我们进行了肽组学分析，以描绘人类棕色脂肪细胞在暴露于产热刺激时释放的细胞外肽。具体来说，我们鉴定出一种以细胞自主方式调节脂肪细胞产热的分泌肽，并将其命名为 BATSP1。BATSP1 促进 BAT 产热，并在体内诱导白色脂肪组织的褐色化，导致在冷应激下能量消耗增加。BATSP1 处理可预防高脂肪饮食诱导的肥胖，并改善葡萄糖耐量和胰岛素抵抗。在机制上，BATSP1 促进了叉头框转录因子 1（FOXO1）的核质穿梭，并释放其对解偶联蛋白 1（UCP1）的转录抑制。总的来说，我们对急性 forskolin（FSK）刺激后的人类棕色脂肪细胞细胞外肽组进行了全面分析，并将 BATSP1 鉴定为一种新的产热调节剂，它可能为肥胖症的治疗提供一种潜在的方法。
