棕色脂肪组织产热功能的胞外调控机制

Extracellular regulatory mechanisms of brown adipose tissue thermogenesis

摘要:

当机体能量摄入长期大于消耗时,会诱发肥胖。非颤抖产热介导的能量消耗是改善能量稳态、治疗肥胖的重要靶点。棕色脂肪组织(BAT)是非颤抖产热的主要位点,其功能受到多个系统的调控。本文综述了BAT产热的胞外调控机制:神经系统通过中枢-交感神经轴整合寒冷与代谢信号,下丘脑神经环路感应脂质与激素状态,动态调节BAT产热阈值；免疫系统中,巨噬细胞通过极化动态、分泌组重塑和线粒体转移参与代谢调控,肥大细胞和T细胞亚群通过细胞因子网络双向调节BAT微环境；消化系统通过胃肠激素[胰泌素、胆汁酸、胆囊收缩素、胰高血糖素样肽1(GLP-1)等]、肝脏分泌蛋白[妊娠带蛋白(PZP)、成纤维细胞生长因子21(FGF21)]和代谢产物,以及肠道微生物群的代谢产物(短链脂肪酸、胆汁酸)影响BAT产热；自分泌和旁分泌机制中,BAT通过分泌肌生长抑制素、鸢尾素、线粒体细胞外囊泡、血管内皮生长因子α(VEGF-α)、FGF21和神经调节蛋白4等进行局部调控。此外,BAT激活可通过脂质清除、抗炎和分泌脂肪因子等机制延缓动脉粥样硬化进展。本文系统梳理了BAT产热的胞外调控网络,为代谢性疾病防治提供理论基础和潜在干预靶点。

Abstract:

When long-term energy intake exceeds energy expenditure, obesity is induced. Energy expenditure driven by non-shivering thermogenesis is an important target for improving energy homeostasis and treating obesity. Brown adipose tissue (BAT) is the primary site of non-shivering thermogenesis, and its function is regulated by multiple systems through extracellular mechanisms. This review summarizes the extracellular regulatory mechanisms of BAT thermogenesis:the nervous system integrates cold and metabolic signals through the central-sympathetic neural axis, and hypothalamic neural circuits sense lipid and hormonal states to dynamically adjust BAT thermogenic thresholds. In the immune system, macrophages participate in metabolic regulation through polarization dynamics, secretome remodeling and mitochondrial transfer, while mast cells and T cell subsets bidirectionally regulate the BAT microenvironment through cytokine networks.The digestive system influences BAT thermogenesis through gastrointestinal hormones (secretin, bile acids, cholecystokinin, glucagon-like peptide-1 (GLP-1), etc.), liver-secreted proteins (pregnancy zone protein(PZP), fibroblast growth factor 21 (FGF21) and metabolites, as well as gut microbiota-derived metabolites (short-chain fatty acids, bile acids). In autocrine and paracrine mechanisms, BAT performs local regulation by secreting myostatin, irisin, mitochondrial extracellular vesicle, vascular endothelial growth factor-α (VEGF-α), fibroblast growth factor 21 (FGF21), and neuregulin 4. Additionally, BAT activation can delay atherosclerosis progression through mechanisms including lipid clearance, anti-inflammatory effects, and adipokine secretion. This review systematically outlines the extracellular regulatory network of BAT thermogenesis, providing a theoretical foundation and potential intervention targets for the prevention and treatment of metabolic diseases.