Yan Chenxu, Burley George, Gao Hanyu, Shi Yan-Chuan
Neuroendocrinology Group, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, NSW 2010, Australia.
Faculty of Medicine and Health, UNSW Sydney, Sydney 2052, Australia.
Endocrinology. 2025 Jul 8;166(9). doi: 10.1210/endocr/bqaf118.
Brown adipose tissue (BAT), traditionally recognized for its role in thermogenesis, has emerged as an active endocrine organ that coordinates systemic energy expenditure with glucose homeostasis. This review explores the emerging concept of bidirectional crosstalk between BAT and pancreatic β-cells, focusing on potential mechanisms through which BAT may regulate insulin secretion and β-cell survival. In addition to its thermogenic function, BAT serves as a metabolic sink and secretes various hormones (batokines), metabolites, and exosomes that can influence β-cell function directly or indirectly. Key batokines such as fibroblast growth factor 21, IL-6, ependymin-related protein 1, neuregulin 4, and phospholipid-transfer protein have shown potential in the preservation of β-cell health, although their clinical relevance requires further investigation. Emerging evidence also points to BAT-derived exosomes and microRNAs, including miR-26a, as novel regulators of insulin secretion. Neural mechanisms may contribute to this interorgan communication via sympathetic and sensory innervation, and BAT-derived neurotrophic factors may modulate autonomic inputs to peripheral tissues, including the pancreas. Conversely, β-cells influence BAT activation via hormonal (eg, insulin, glucagon), exosomal, and central pathways, forming a proposed BAT-brain-islet axis. This bidirectional communication appears disrupted in obesity and diabetes, where BAT dysfunction and β-cell stress exacerbate metabolic decline. Despite growing interest, mechanistic insights into BAT-islet crosstalk remain incomplete. Future research using omics technologies, co-culture systems, and in vivo manipulation models will be critical to identify novel mediators and clarify their roles in metabolic regulation. Understanding this interorgan communication may offer new therapeutic avenues for obesity and diabetes.
棕色脂肪组织（BAT）传统上因其在产热中的作用而被认可，如今已成为一个活跃的内分泌器官，可协调全身能量消耗与葡萄糖稳态。本综述探讨了BAT与胰腺β细胞之间双向串扰这一新兴概念，重点关注BAT可能调节胰岛素分泌和β细胞存活的潜在机制。除了其产热功能外，BAT还作为一个代谢库，分泌各种激素（棕色脂肪组织因子）、代谢物和外泌体，这些物质可直接或间接影响β细胞功能。关键的棕色脂肪组织因子，如成纤维细胞生长因子21、白细胞介素-6、室管膜素相关蛋白1、神经调节蛋白4和磷脂转运蛋白，已显示出在保护β细胞健康方面的潜力，尽管它们的临床相关性还需要进一步研究。新出现的证据还指出，BAT衍生的外泌体和微小RNA，包括miR-26a，是胰岛素分泌的新型调节因子。神经机制可能通过交感神经和感觉神经支配促进这种器官间的通信，并且BAT衍生的神经营养因子可能调节对外周组织（包括胰腺）的自主神经输入。相反，β细胞通过激素（如胰岛素、胰高血糖素）、外泌体和中枢途径影响BAT激活，形成一个拟议的BAT-脑-胰岛轴。这种双向通信在肥胖症和糖尿病中似乎被破坏，其中BAT功能障碍和β细胞应激会加剧代谢衰退。尽管人们的兴趣日益浓厚，但对BAT-胰岛串扰的机制性认识仍然不完整。未来使用组学技术、共培养系统和体内操作模型的研究对于识别新的介质并阐明它们在代谢调节中的作用至关重要。了解这种器官间的通信可能为肥胖症和糖尿病提供新的治疗途径。
