ELOVL3对机体非颤抖产热功能的调节作用及其机制研究

非颤抖产热对维持体温和能量代谢稳态具有重要意义，在减重和改善代谢性疾病中的潜在作用深受关注。极长链脂肪酸延长酶3（Elovl3）催化C20-C24脂肪酸的合成，在棕色脂肪动员和白色脂肪棕色化过程中表达急剧上调，被作为棕色脂肪和米色脂肪细胞的标志分子，但其在寒冷耐受和产热中的作用尚不明确。我们前期建立了脂肪细胞特异性敲除Elovl3的小鼠模型，发现Elovl3缺失导致小鼠耐寒能力明显受损、棕色脂肪产热功能障碍，伴有产热基因表达下调、线粒体功能相关的心磷脂含量降低；而对白色脂肪棕色化无明显影响。本项目拟在上述工作基础上，鉴定棕色脂肪中Elovl3调节线粒体产热功能的关键中间代谢产物，揭示其调节产热的细胞分子机制，为肥胖相关疾病的干预和治疗提供新的思路和药物靶点，可望形成原创性科研成果。

Non-shivering thermogenesis plays an important role in maintaining body temperature and energy homeostasis, and its potential role in weight loss and improving metabolic diseases has attracted much attention. Elongation of very long chain fatty acids Protein 3 (Elovl3), which catalyzes the synthesis of C20-C24 fatty acids, is up-regulated in the process of brown adipose tissue mobilization and white adipose tissue browning, but the specific role of Elovl3 in thermogenesis is not clear. We previously generated two mouse models with Elovl3-specific deleted in brown adipose tissue or whole adipose tissue. Elovl3 deletion in brown adipose tissue led to a cold intolerant and brown adipose tissue thermogenic dysfunction phenotype, and the absence of Elovl3 in BAT significantly down-regulated the levels of thermogenic genes and the content of cardiolipin. Surprisingly, Elovl3 deletion in white adipose tissue showed no impact on the browning of white adipose tissue. Based on the above work, this project intends to identify the key intermediate metabolites of elovl3 in brown adipose tissue that regulate mitochondrial thermogenesis, reveal the cellular and molecular mechanism of thermogenesis by Elovl3, provide new ideas and drug targets for the intervention and treatment of obesity-related diseases, and form original scientific research achievements.