新型SIRT1激活剂XZG2151对3T3-L1前脂肪细胞分化的影响

Effect of a novel SIRT1 activator XZG2151 on the differentiation of 3T3-L1 preadipocytes

目的探讨新型沉默信息调节因子2相关酶1(SIRT1)激活剂化合物XZG2151对3T3-L1前脂肪细胞分化的影响。方法将3T3-L1前脂肪细胞分成4组:3T3-L1细胞组(Pre组)、DMSO组(Ctrl组)、阳性对照组(SRT2104组)、实验组(XZG2151组)。采用CCK8法检测XZG2151对3T3-L1细胞增殖的影响。油红O染色法、甘油含量测定法观察XZG2151对3T3-L1细胞中脂肪形成的影响。实时荧光定量PCR及蛋白质免疫印迹法检测XZG2151对3T3-L1细胞分化过程中相关基因和蛋白表达水平的影响。结果10μmol/L XZG2151对3T3-L1前脂肪细胞的增殖无显著影响(P>0.05)。与Ctrl组相比,SRT2104组和XZG2151组3T3-L1细胞脂肪含量显著降低(P<0.05)。与Ctrl组相比,XZG2151组SIRT1、激素敏感脂肪酶(HSL)、肉毒碱棕榈酰基转移酶1A(CPT1A)的mRNA表达水平显著升高(P<0.05);脂肪合成转录因子PPARγ和C/EBPβ、硬脂酰辅酶A去饱和酶(SCD)、乙酰辅酶A羟化酶(ACC)、脂肪酸合成酶(FASN)的mRNA表达水平显著下降(P<0.05)。此外,与Ctrl组相比,XZG2151组SIRT1、p-ACC、CPT1A蛋白表达显著升高(P<0.05),FASN蛋白表达显著下降(P<0.05)。结论XZG2151可调节3T3-L1前脂肪细胞的脂肪生成和脂质代谢,从而抑制前脂肪细胞分化。

Objective To investigate the effect of a novel silencing information regulator 2 related enzyme 1(SIRT1)activator XZG2151 on the differentiation of 3T3-L1 preadipocytes.Methods 3T3-L1 preadipocytes were divided into four groups:a 3T3-L1 preadipocyte group(group Pre),a DMSO group(group Ctrl),a positive control group(group SRT2104),and an experimental group(group XZG2151).The proliferation of 3T3-L1 cells was detected by CCK8 assay.The relevant lipid content in 3T3-L1 cells was detected by red oil O staining and glycerol content assay.The mRNA and protein expression of indicators related to the differentiation of 3T3-L1 cells were detected by real-time fluorescence quantitative PCR and Western blot.Results Treatment with XZG2151 at 10μmol/L exerted no significant effect on the proliferation of 3T3-L1 preadipocytes(P>0.05).Compared with group Pre,the relevant lipid content significantly decreased in groups SRT2104 and XZG2151(P<0.05).Compared with group Ctrl,group XZG2151 showed remarkable increases in the mRNA levels of SIRT1,hormone-sensitive lipase(HSL)and carnitine palmitoyltransferase 1A(CPT1A)(P<0.05);and decreases in the mRNA levels of transcription factors PPARγand C/EBPβ,stearoyl-CoA desaturase(SCD),acetyl-CoA carboxylase(ACC)and fatty acid synthase(FASN)(P<0.05).Furthermore,compared with group Ctrl,group XZG2151 showed significant increases in the protein expression of SIRT1,p-ACC and CPT1A(P<0.05),and decreases in the protein expression of FASN(P<0.05).Conclusions XZG2151 can regulate adipogenesis and lipid metabolism in 3T3-L1 preadipocytes,thereby inhibiting preadipocyte differentiation.