棕色脂肪分泌肽BATSP1促白色脂肪棕色化的作用与机制研究

Inducing white adipocytes browning has been developed as a very promising strategy for obesity treatment. Based on the new understandings that brown fat is not only a heat-generating organ but also a secretory organ, we successfully identified a novel brown fat-enriched secreted peptide BATSP1 which could promote white adipocytes browning. The results of bioinformatics analysis (Zdock etc.) and peptide Pull-down assay showed that the function and mechanism was closely associated with RXRα, suggesting BATSP1 may promote white adipocytes browning through the interaction with RXRα. To properly evaluate the role of BATSP1, we verify its function and mechanism in various cell and animal models. And to systematically demonstrate the interaction between BATSP1 and RXRα, physical and biological methods are performed. We also optimize the physicochemical properties of BATSP1 to enhance its effect in promoting white adipocytes browning, then to deeply evaluate the possibility and feasibility of BATSP1 in obesity treatment. If successful, BATSP1 is expected to be peptide drug for obesity treatment, and to provide new ideas for study and application of brown fat-enriched secreted peptide in promoting white adipocytes browning and obesity treatment, all of which with strong innovation and transformation prospect.

诱导白色脂肪棕色化已成为极具前景的肥胖治疗新策略。基于棕色脂肪不仅是产热器官更是分泌器官的新认识，我们从棕色脂肪细胞分泌成分中成功获得一条新的、具有显著促白色脂肪棕色化的多肽BATSP1，通过Zdock等生物信息学方法与多肽Pull down实验显示BATSP1作用机制与RXRα密切相关，提示BATSP1可能通过RXRα机制促白色脂肪棕色化。本研究拟应用细胞、动物模型全面评估BATSP1的功能与机制，通过物理学、生物学方法系统论证BATSP1与RXRα蛋白之间的相互关系，并优化BATSP1理化性质，以增强BATSP1的促白色脂肪棕色化作用，从而深入评估BATSP1作为肥胖治疗手段的可能性与可行性。研究如获成功，BATSP1有望成为肥胖治疗的多肽药物，并为棕色脂肪分泌多肽在促白色脂肪棕色化、肥胖治疗中的研究与应用提供新思路，因此具有较强的创新性与转化前景。

肥胖是以脂肪组织异常积聚为特征的一类疾病，可引起各类严重并发症，严重威胁人类健康。棕色脂肪可通过增加能量消耗而减轻体重，白色脂肪也可以转化为“棕色化”状态，因此诱导白色脂肪细胞棕色化已成为极具前景的肥胖治疗新策略。.基于棕色脂肪不仅是产热器官更是分泌器官的新认识，我们从棕色脂肪细胞分泌成分中成功新发现一条具有显著促脂肪组织棕色化多肽BATSP1（Brown Adipose Tissue Secreted Peptide 1）。本研究发现BATSP1可以促进脂肪组织棕色化，增加线粒体数量，显著增强小鼠产热能力；进而在肥胖动物模型中，我们发现BATSP1干预后脂肪组织发生棕色化水平显著增强，小鼠体重显著下降，糖脂代谢紊乱得到显著改善；我们还发现，BATSP1 联合低温干预下具有更显著抵抗 HFD 诱导肥胖的作用；BATSP1作用机制可能是其与 FOXO1 结合，增强其磷酸化水平，促进FOXO1核向质的转移，进而增强产热功能。.本研究应用细胞、动物模型初步阐明了BATSP1的功能与机制，提示BATSP1作为肥胖治疗手段具有一定的可能性与可行性，进一步研究开发BATSP1，有望为肥胖防治提供新的治疗手段。