Sfrp5 interacts with Slurp1 to regulate the accumulation of triglycerides in hepatocyte steatosis model.

Secreted frizzled-related protein 5 (Sfrp5), an anti-inflammatory adipocytokine secreted by adipocytes, plays an important role in energy metabolism. Studies have shown that Sfrp5 plays a salutary role in the regulation of lipid metabolism, but its specific mechanism needs further study. In this study, we showed a lower level of Sfrp5 in subjects with diet-induced obesity than in normal-diet C57BL/6J mice. To further investigate Sfrp5-associated proteins in HepG2 cells, the immunoprecipitation assay and silver staining assay were performed. By mass spectrometry analysis, secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide (Slurp-1) was found to interact with Sfrp5. Further verification was obtained through the positive and reverse immunoprecipitation assay. In this study, we found that the sole over-expression of Slurp1 promoted the expression of Sfrp5 in palmitate-induced HepG2 cells. In addition, our experimental evidence shows that the role of Slurp1 in decreasing TG level was greatly reduced in the case of suppression of expression of Sfrp5 in palmitate-induced model cells. Our study further found that Slurp1 regulates the synthesis pathway of triglyceride by interacting with Sfrp5 to alleviate triglyceride accumulation in palmitate-induced model cells. In summary, we are the first to discover the interaction between Sfrp5 and Slurp1, and we found that Slurp1 may regulate the accumulation of TG through Sfrp5.