Multi tissue proteomic analysis of cold exposure

This study explored the proteomic basis of cold adaptation, quantifying 11,394 proteins across 6 metabolic tissues and plasma. Systems level analysis revealed an enrichment for proteins involved in metabolism. In brown adipose tissue (BAT), cold adaptation was associated with enhanced glucose utilisation, including select remodelling of upper glycolysis to enhance superoxide production and UCP1 activity, and a downregulation of proteins involved in fatty acid oxidation. Strikingly, opposite changes were observed in liver and white adipose tissues, including upregulation of proteins involved in gluconeogenesis and lipolysis, respectively. This suggests that coordinated changes in many organs are required for maximal BAT thermogenesis. This coordination also associated with cold-regulated alterations to the plasma proteome, including elevated Fetuin A that is consistent with enhanced lipolysis in white adipose. Finally, overlapping but inverse changes in cold-exposed and diet-induced obese mice support impaired BAT activity as a driver of obesity.

本研究围绕冷适应的蛋白质组学基础展开探索，对6种代谢组织及血浆中的11394种蛋白质进行了定量分析。系统层面分析显示，参与代谢过程的蛋白质呈现富集现象。在棕色脂肪组织（brown adipose tissue, BAT）中，冷适应与葡萄糖利用增强相关，具体表现为糖酵解上游通路的选择性重塑，以提升超氧化物生成与解偶联蛋白1（UCP1）活性，同时下调参与脂肪酸氧化的蛋白质。值得注意的是，肝脏与白色脂肪组织中则呈现相反的变化：前者上调参与糖异生的蛋白质，后者则上调参与脂解的蛋白质。这表明，要实现最佳的棕色脂肪组织产热功能，需要多个器官发生协同变化。这种协调调控还与血浆蛋白质组的冷诱导改变相关，其中胎球蛋白A（Fetuin A）水平升高，这与白色脂肪组织中增强的脂解作用相符。最后，冷暴露小鼠与饮食诱导肥胖小鼠体内存在重叠但方向相反的变化，这支持了“棕色脂肪组织活性受损是肥胖的致病驱动因素”这一结论。