Beclin1的乙酰化调控及对脂肪细胞分化与代谢的作用研究

Obesity is fundamentally a problem of energy balance, including the increase of capacity and number of adipocytes, resulting in the abnormal accumulation of lipid in other tissues. Autophagy plays an important role in cell self-renewal and maintaining energy balance. Studies found that autophagy can regulate lipid metabolism. Beclin1 is an important autophagy related protein, which regulates autophagosome from formation to maturation. We also found that Beclin1 is an important target for autophagy in adipocytes. Furthermore, we found that the acetylation of Beclin1 was increased in obesity mice model. We also found that acetylation of Beclin1 increases its acetylation and its stabilit. So we speculate Beclin1 acetylation can regulate adipocytes differentiation and dynamic equilibrium of lipid metabolism by affecting autophagy. We will detect the effect of Beclin1 acetylation on autophagy, and we will exam how Beclin1 acetylation regulate adipocytes differentiation and dynamic equilibrium of lipid metabolism by conducting point mutation lentivirious，so as to find a potential target of treating obesity.

肥胖是伴随能量稳态失衡出现的体内脂肪过度累积，包括脂肪细胞数量增加和体积增大，脂质异位沉积。自噬在细胞自我更新和维持能量平衡中发挥重要作用，大量研究发现自噬可以调控脂肪代谢。Beclin1是重要的自噬相关蛋白，调控自噬泡形成到成熟的整个过程，我们的研究发现Beclin1介导的自噬在整体水平参与能量代谢；我们还发现肥胖小鼠模型中Beclin1乙酰化水平增加，且在细胞水平发现乙酰化修饰大大增加Beclin1的蛋白稳定性。因此，我们猜测Beclin1乙酰化可以通过影响自噬调控脂肪细胞分化和代谢，我们将从从细胞和整体水平阐述Beclin1乙酰化修饰对自噬的调控，通过构建乙酰化位点突变的慢病毒进一步研究Beclin1乙酰化对脂肪细胞分化和代谢的作用，为肥胖及相关疾病的治疗提供潜在的靶点。

肥胖是伴随能量稳态失衡出现的体内脂肪过度累积，肥胖个体脂肪组织内脂滴过度沉积，从而导致脂质异位沉积在其他组织。大量文献研究发现自噬可以调控脂肪代谢，包括脂肪细胞分化和脂解等。Beclin1是重要的自噬相关蛋白，调控自噬泡形成到成熟的整个过程，参与运动导致的自噬增加的获益。我们发现Belcin1是脂肪细胞自噬的重要调控靶点。我们发现在高脂小鼠模型和脂肪细胞分化及脂解过程中Beclin1乙酰化水平升高，我们用免疫共沉淀的方法发现成熟脂肪细胞中Beclin1存在乙酰化修饰，且乙酰化后可通过影响Beclin1的蛋白稳定性影响自噬。我们通过软件预测及构建乙酰化位点突变慢病毒的研究方法发现了新的Beclin1乙酰化位点K414，进一步发现该乙酰化位点可以调控脂肪细胞自噬，脂肪细胞分化及脂肪分解。Beclin1乙酰化位点及对脂肪代谢调控的研究，这对于探讨自噬对脂质动态平衡及全身能量代谢的调节作用具有重要意义，且为肥胖及相关疾病的治疗提供新的思路和靶点。