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

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 10 μmol/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 PPARγ and 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.