棕色脂肪分泌肽BSPFL1改善非酒精性脂肪肝的作用与机制研究

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by hepatocyte steatosis and excessive lipid accumulation, which poses a serious threat to human health. Unfortunately, there is no available medicine untill now. Recent studies have shown that brown adipose tissue (BAT) is an important endocrine organ, and the secretions play crucial role in the regulation of hepatic lipid metabolism. BSPFL1, a functional peptide obtained from the secretory components of BAT, has not been reported before. In the preliminary study, we found that BSPFL1 could inhibit the expression of genes related to hepatic lipogenesis, reduce lipid accumulation and alleviate the phenotype of NAFLD. Mechanistically, BSPFL1 may function by regulating the PI3K-Akt signaling pathway. Thus, this project will systematically evaluate the consistency of BSPFL1 in inhibiting lipid synthesis in liver cells of different species. Then, the role and mechanism of BSPFL1 in improving the phenotype of NAFLD will be comprehensively verified. More importantly, the molecular mechanism of BSPFL1 will be further elucidatd by taking the PI3K-Akt signaling pathway as a clue. If this study is successful, it is expected to provide a new method for the treatment of NAFLD, with potential clinical value and social significance.

非酒精性脂肪肝（NAFLD）是以肝细胞脂肪变性以及脂质过度累积为主要特征的代谢性疾病，严重威胁人类健康，目前尚无理想的治疗药物。近年来研究发现，棕色脂肪组织（BAT）作为内分泌器官，其分泌组分在肝脏脂质代谢调控中发挥重要作用。我们利用多肽组学手段从BAT分泌组分中筛选获得一条功能未知的多肽BSPFL1，初步研究证实，BSPFL1能够抑制肝脏脂质合成基因的表达，降低脂质堆积，改善NAFLD表型；BSPFL1可能通过调控PI3K-Akt信号通路发挥作用。本课题拟在前期研究基础上，系统评估BSPFL1在不同种属肝细胞中抑制脂质合成的功能一致性；全面验证BSPFL1改善NAFLD表型的作用与机制；以PI3K-Akt信号通路为线索，深入阐明BSPFL1发挥作用的分子机制。本研究若获成功，将有望为NAFLD的治疗提供新手段，具有潜在的临床价值和社会意义。

非酒精性脂肪肝（NAFLD）是以肝细胞脂肪变性以及脂质过度累积为主要特征的代谢性疾病，严重威胁人类健康，目前尚无理想的治疗药物。近年来研究发现，棕色脂肪组织（BAT）作为内分泌器官，其分泌组分在肝脏脂质代谢调控中发挥重要作用。.本项目主要研究发现：① 筛选获得多肽BSPFL1，具有分子量低、稳定性好、亲脂性高、易于入胞等优势，目前未见相关功能报道。② 细胞水平研究发现，BSPFL1可抑制肝细胞中脂质合成基因表达、促进脂质分解、降低细胞内脂质堆积；③ 动物实验发现，BSPFL1可以抑制肝脏脂质合成，改善NAFLD表型；④ 机制探索发现，BSPFL1可能通过调控PI3K-Akt信号通路发挥生物学功能，为NAFLD的治疗提供新的理论依据。.小分子多肽具有毒性低、特异性强、生产成本低等独特优势，有望成为药物研发的最佳选择，具有潜在的经济价值和社会意义。