肥大细胞调控小鼠脂肪组织棕脂化和产热的机制研究

脂肪组织棕脂化活性的诱导，已被视为改善肥胖及其并发症一个重要策略。我们前期研究显示，在室温低脂饮食小鼠中，肥大细胞源5-HT可能关键性地抑制了皮下脂肪组织棕脂化，从而调控了能量代谢。但是，对于在多种代谢相关生理状态下，肥大细胞调控脂肪组织棕脂化和产热的作用以及其细胞生物学机制并不了解。本项目拟在此基础上，利用肥大细胞缺失、稳定和再回复小鼠，全面研究在室温、冷刺激、热中性和高脂饮食条件下肥大细胞调控机体能量代谢的作用，明确肥大细胞对于这些生理状态下的各部位脂肪组织棕脂化和产热的影响。利用分子和细胞生物学技术手段,于体内体外深入研究肥大细胞调控室温低脂饮食小鼠皮下脂肪组织棕脂化和产热的机制，并检验这些机制是否适用于肥大细胞在其它生理状态下对于脂肪组织棕脂化和产热的可能作用。该项目的执行,不仅能丰富肥大细胞调控脂肪组织棕脂化的细胞生物学理论，而且也能为肥胖及其并发症的治疗和药物设计提供新的思路。

The preferential induction of adipose tissue browning and thermogenesis has been regarded as an important strategy to ameliorating obesity and associated complications. Our previous studies showed that mast cell-derived 5-HT might critically inhibit browning and thermogenesis in subcutaneous adipose tissues (SAT) and hereby regulated energy expenditure in low fat diet (LFD)-fed mice. However, the comprehensive effects of mast cells on adipose tissue browning and thermogenesis in various metabolism-associated physiology and their possible regulatory mechanisms remain unclear. Therefore, based on the pervious findings, we will utilizing mast cell deficient, stabilized and reconstituted mice to investigate the involvements of mast cells in energy expenditure. Firstly, metabolic rates will be detected in mice with room temperature, cold acclimatization, thermoneutrality and high-fat diet (HFD), respectively. Secondly, the relevant alterations in browning and thermogenesis will be assessed in various adipose tissues, including SAT, epididymal adipose tissues (EAT) and brown adipose tissues (BAT). Further, utilizing molecular and cellular methods, we will explore the detailed mechanisms of mast cells regulating SAT browning and thermogenesis in LFD-fed mice. Finally, the mechanisms will be confirmed in cold-acclimatized, thermoneutral, and HFD-fed mice. The proposal will not only give us more cell biological knowledge about the role of mast cells in obesity and associated complications, but also suggest a new therapeutic approach for these common diseases.