State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People's Republic of China.
Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People's Republic of China.
Stem Cells Transl Med. 2024 Oct 10;13(10):985-1000. doi: 10.1093/stcltm/szae056.
Exploration of factors originating from brown adipose tissue that govern the thermogenic adipocyte differentiation is imperative for comprehending the regulatory framework underlying brown fat biogenesis and for devising therapeutic approaches for metabolic disorders associated with obesity. Prior evidence has illuminated the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating thermogenesis within adipose tissue. Here, we aimed to explore and identify the critical lncRNA that could promote thermogenic adipocyte differentiation and to provide a novel strategy to treat obesity-related metabolic diseases in the future. In this study, through amalgamation with our previous lncRNA microarray data from small extracellular vesicles derived from BAT (sEV-BAT), we have identified sEV-BAT-enriched lncRNA AK029592 as a critical constituent of the thermogenic program, which actively fostered beige adipocyte differentiation and enhanced the thermogenic capacities of adipose tissue. Moreover, lncRNA AK029592 could sponge miR-199a-5p in adipocytes to stimulate thermogenic gene expression. Consequently, we concluded lncRNA AK029592 as a crucial lncRNA component of the thermogenic program that regulated beige adipocyte differentiation and white adipose tissue browning, thereby providing a novel therapeutic target and strategy in combating obesity and related metabolic diseases.
探索源自棕色脂肪组织的调控脂肪细胞产热分化的因素，对于理解棕色脂肪生成的调控机制以及制定与肥胖相关代谢紊乱的治疗方法至关重要。先前的证据表明长非编码 RNA（lncRNA）在调节脂肪组织产热中起着关键作用。在这里，我们旨在探索和鉴定能够促进产热脂肪细胞分化的关键 lncRNA，并为未来治疗肥胖相关代谢疾病提供新的策略。在这项研究中，我们通过将之前从小鼠棕色脂肪组织来源的外泌体（sEV-BAT）中获得的 lncRNA 微阵列数据与我们的研究结果相结合，鉴定出 sEV-BAT 中富含的 lncRNA AK029592 是产热程序的关键组成部分，它可以积极促进米色脂肪细胞分化，并增强脂肪组织的产热能力。此外，lncRNA AK029592 可以在脂肪细胞中海绵吸附 miR-199a-5p 来刺激产热基因的表达。因此，我们得出结论，lncRNA AK029592 是产热程序的关键 lncRNA 组成部分，它调节米色脂肪细胞分化和白色脂肪组织棕色化，从而为肥胖症和相关代谢疾病的治疗提供了新的靶点和策略。
