AIM:To investigate the effects of glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 on white adipose tissue (WAT) and the underlying mechanisms.METHODS:Male C57BL/6J mice (8 weeks) were chal-lenged by high-fat diet for 12 weeks, and were randomly divided into saline group and exendin-4 group.The mRNA expres-sion of sirtuin 1 (SIRT1), adipose triglyceride lipase (ATGL), TNF-αand adiponectin of WAT was detected by real-time PCR.3T3-L1 adipocytes or mouse embryonic fibroblasts cells were treated with exendin-4 for 24 h.The protein levels of SIRT1, ATGL and hormone-sensitive lipase (HSL) were determined by Western blot.RESULTS:Exendin-4 significantly decreased epididymal fat weight, fasting blood glucose and serum triglyceride levels ( P<0.05) , and reduced body weight and serum TNF-αlevel.The mRNA expression of SIRT1, ATGL and adiponectin in WAT was all significantly up-regulated by exendin-4, which were contrary to the down-regulation of TNF-αmRNA expression (P<0.05).Exendin-4 promoted the protein expression of SIRT1, ATGL, and HSL in 3T3-L1 adipocytes in a dose-dependent manner.Less lipid droplets with up-regulation of lipolytic protein expression were observed when combined with SIRT1 agonist treatment, which were suppressed by SIRT1 inhibitor.Deletion of SIRT1 led to larger adipocytes with more lipid droplets, and the effect of ex-endin-4 on the lipolysis disappeared when SIRT1 was deficient.CONCLUSION:Exendin-4 promotes lipolysis in WAT of obese mice via activation of SIRT1.

Objective To investigate the effect of EP4 gene silencing on the growth and migration of K1 cells. Methods K1 cells with stable knockdown of EP4 were constructed with lentiviral vector. QRT-PCR and western blot analysis were used to detect the expression of EP4 mRNA and protein in K1 cells. CCK8 assay and flow cytometry were employed to measure cell viability and apoptosis. Transwell assay was applied to detect cell migration. Results Compared with the negative control group,the mRNA and protein expression of EP4 were sig-nificantly decreased in K1 cells with stable knockdown of EP4. Furthermore,shRNA-mediated silencing of EP4 gene remarkably suppressed cell viability and induced apoptosis of K1 cells.The migration of K1 cells with knock-down of EP4 was decreased compared with the negative control group. Conclusions EP4 gene silencing can in-hibit growth and induce apoptosis of K1 cells.Downregulation of EP4 can significantly reduce migration of K1 cells.