Gene expression Analysis of wild type (WT) and Blnc1 adipose specific transgenic mice (Tg) epididymal WAT (eWAT) Transcriptomes after 21 weeks high fat diet (HFD) feeding. Gene expression Analysis of wild type (WT) and Blnc1 adipose specific transgenic mice (Tg) epididymal WAT (eWAT) Transcriptomes after 21 weeks high fat diet (HFD) feeding

Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of adipocyte differentiation and gene expression. However, their physiological role in adipose tissue biology and systemic energy metabolism has not been established. Here we show that adipose tissue expression of Blnc1, a conserved lncRNA regulator of thermogenic genes, is highly induced in obese mice. Fat-specific inactivation of Blnc1 impairs cold-induced thermogenesis and browning, exacerbates obesity-associated brown fat whitening, and worsens adipose tissue inflammation and fibrosis, leading to more severe insulin resistance and hepatic steatosis. On the contrary, transgenic expression of Blnc1 in adipose tissue elicits the opposite and beneficial metabolic effects, supporting a critical role of Blnc1 in driving adipose adaptation during obesity. Mechanistically, Blnc1 cell-autonomously attenuates proinflammatory cytokine signaling and promotes fuel storage in adipocytes through its protein partner Zbtb7b. This study illustrates a surprisingly pleiotropic and dominant role of lncRNA in driving adaptive adipose tissue remodeling and preserving metabolic health. Overall design: eWAT mRNA profiles of WT and Blnc1 adipose specific Tg mice after 21 weeks HFD feeding were generated by microarray, in triplicate

长链非编码RNA（long noncoding RNAs，lncRNAs）是一类逐渐受到关注的强效脂肪细胞分化与基因表达调控因子。然而，其在脂肪组织生物学及系统性能量代谢中的生理功能尚未明确。本研究发现，产热基因保守lncRNA调控因子Blnc1在肥胖小鼠的脂肪组织中表达显著上调。脂肪组织特异性敲除Blnc1会损伤冷诱导产热与脂肪褐变过程，加剧肥胖相关的棕色脂肪白色化，加重脂肪组织炎症与纤维化，进而导致更严重的胰岛素抵抗与肝脂肪变性。与之相反，在脂肪组织中过表达Blnc1则会产生相反的有益代谢效应，证实Blnc1在肥胖过程中驱动脂肪组织适应方面发挥关键作用。机制层面，Blnc1可通过细胞自主方式与其蛋白伴侣Zbtb7b结合，抑制促炎细胞因子信号通路，并促进脂肪细胞内的燃料储存。本研究揭示了lncRNA在驱动适应性脂肪组织重塑与维持代谢健康中出人意料的多效性与主导性作用。整体实验设计：对野生型（wild type，WT）与脂肪组织特异性过表达Blnc1的转基因（transgenic，Tg）小鼠，在高脂饮食（high-fat diet，HFD）喂养21周后，通过微阵列技术（microarray）检测其附睾白色脂肪组织（epididymal white adipose tissue，eWAT）的mRNA表达谱，每组设置3个生物学重复。