Liang Chen -, Yu Han -, Jing Li -, Chunpeng Feng -, Chen Chen -, Ting Ye -
Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Hospital Administration Office, China Academy of Chinese Medical Sciences, Beijing, China.
Pak J Pharm Sci. 2023 May;36(3):773-782.
PPARγ, CEBP/α, and SREBP1C are the major transcriptional factors participating in adipogenesis and lipogenesis. SIRT1 and IGF-1 signaling pathways are important pathways involved in body endocrine and metabolism. Our unique Chinese herbal medicine Xiao-Gao-Jiang-Zhuo (XGJZ) has a remarkable clinical effect on obesity. However, the molecular basis remains unknown. XGJZ-containing serum was treated in the incubation of 3T3-L1 preadipocytes to observe its function in the 3T3-L1 cell differentiation. Oil Red O staining was used to monitor the lipid droplets accumulated after 8 days of incubation. RT-qPCR and western blotting were used to investigate the regulatory effects of XGJZ-containing serum on adipogenesis-related factors. The protein levels of main molecules in SIRT1 and IGF-1 signaling pathways were also detected by western blotting. XGJZ-containing serum notably suppressed the lipid accumulation in differentiated adipocytes through SIRT1/IGF-1 pathway. XGJZ-containing serum activated the SIRT1/IGF-1 pathway and reduced the expression levels of PPARγ, CEBP/α, and SREBP1C through this pathway. Additionally, XGJZ-containing serum enhanced the phosphorylation of ATGL and HSL and then induced lipolysis. XGJZ-containing serum has inhibitory effects on adipogenesis in 3T3-L1 preadipocytes through SIRT1/IGF-1 signaling pathway. Our study affirmed the effect of XGJZ-containing serum in the treatment of obesity. It provides a basis for the mechanism of obesity.
过氧化物酶体增殖物激活受体γ(PPARγ)、CCAAT增强子结合蛋白α(CEBP/α)和固醇调节元件结合蛋白1C(SREBP1C)是参与脂肪生成和脂质生成的主要转录因子。沉默调节蛋白1(SIRT1)和胰岛素样生长因子1(IGF-1)信号通路是参与机体内分泌和代谢的重要通路。我们独特的中药小高降浊(XGJZ)对肥胖具有显著的临床疗效。然而,其分子基础尚不清楚。用含XGJZ的血清处理3T3-L1前脂肪细胞培养物,以观察其在3T3-L1细胞分化中的作用。采用油红O染色监测培养8天后积累的脂滴。采用逆转录定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹法研究含XGJZ血清对脂肪生成相关因子的调控作用。通过蛋白质免疫印迹法还检测了SIRT1和IGF-1信号通路中主要分子的蛋白水平。含XGJZ的血清通过SIRT1/IGF-1通路显著抑制分化脂肪细胞中的脂质积累。含XGJZ的血清激活SIRT1/IGF-1通路,并通过该通路降低PPARγ、CEBP/α和SREBP1C的表达水平。此外,含XGJZ的血清增强了脂肪甘油三酯脂肪酶(ATGL)和激素敏感性脂肪酶(HSL)的磷酸化,进而诱导脂肪分解。含XGJZ的血清通过SIRT1/IGF-1信号通路对3T3-L1前脂肪细胞的脂肪生成具有抑制作用。我们的研究证实了含XGJZ血清在治疗肥胖方面的作用。它为肥胖机制提供了依据。