Table_1_Thermoneutrality-Induced Macrophage Accumulation in Brown Adipose Tissue Does Not Impair the Tissue’s Competence for Cold-Induced Thermogenic Recruitment.xlsx

Brown adipose tissue from mice living under conditions approaching human thermal and nutritional conditions (prolonged exposure to thermoneutral temperature and to an energy-rich (high-fat, high-sugar) diet) — referred to as “physiologically humanized” mice, displays morphological and molecular characteristics significantly different from those observed in young, chow-fed mice maintained at room temperature — referred to as “standard” mice. Here, we further examined brown fat from physiologically humanized and standard mice, as well as from mice exposed to thermoneutrality for a long time but not to an energy-rich diet - referred to here as “long-term thermoneutral” mice. Global transcriptome analysis of brown fat revealed that genes that were the most upregulated in brown fat of thermoneutral mice (both physiologically humanized and long-term thermoneutral) were those related to inflammatory processes, including genes expressed selectively in macrophages. Cellular and molecular analyses confirmed that brown fat from thermoneutral mice was heavily infiltrated by macrophages, predominantly organized into crown-like structures. However, despite this, the brown fat of thermoneutral mice retained full competence to attain the greatest possible recruitment state and became macrophage-depleted during the process of cold acclimation. Thus, profound macrophage accumulation does not influence the thermogenic recruitment competence of brown fat.

长期饲养于接近人类热环境与营养状态条件下的小鼠——即长期暴露于热中性温度（thermoneutral temperature）及高脂高糖能量过剩饮食的小鼠，被称为"生理人源化小鼠（physiologically humanized mice）"——其棕色脂肪组织（brown adipose tissue）的形态与分子特征，与饲养于室温环境、普通饲料喂养的年轻"标准小鼠（standard mice）"存在显著差异。本研究进一步对生理人源化小鼠、标准小鼠，以及长期暴露于热中性环境但未摄入能量过剩饮食的小鼠（本研究中称之为"长期热中性小鼠"）的棕色脂肪组织展开检测分析。对棕色脂肪组织的全局转录组分析（global transcriptome analysis）结果显示，热中性小鼠（包括生理人源化与长期热中性小鼠）的棕色脂肪组织中上调最为显著的基因，均与炎症反应过程相关，其中包含选择性表达于巨噬细胞（macrophage）中的基因。细胞与分子分析证实，热中性小鼠的棕色脂肪组织存在大量巨噬细胞浸润，且这些巨噬细胞主要聚集形成皇冠样结构（crown-like structures）。尽管存在上述巨噬细胞浸润现象，热中性小鼠的棕色脂肪组织仍保留了完整的产热招募能力，在冷驯化（cold acclimation）过程中可完全清除浸润的巨噬细胞。由此可见，大量巨噬细胞聚集并不会影响棕色脂肪组织的产热招募能力。