Effect of stachydrine on high-glucose-induced lipid metabolism in liver cells by regulating the JAK2/STAT3 signaling pathway

LI Yuan; YAO Shuo; DUAN Chao

doi:10.3969/j.issn.1002-7386.2025.07.001

Abstract：Objective To investigate the effect of stachydrine(STA)on high-glucose-induced lipid metabolism in liver cells and its regulatory mechanism on the Janus activated kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods Primary mouse liver cells were isolated and cultured,and they were induced with normal glucose,high glucose,low-dose STA,high-dose STA,high-dose STA+JAK2 inhibitor AG490.Triglycerides(TG)and total cholesterol(TC)in liver cells were measured by enzyme-linked immunosorbent assay(ELISA).Cell viability and lipid aggregation in liver cells were examined by cell counting kit-8(CCK-8)assay and oil red O staining,respectively.Protein levels of key proteins in the JAK2/STAT3 signaling pathway and those associated with lipid metabolism were detected by Western blot.Results Compared with those induced with normal glucose,primary mouse liver cells induced with high glucose had significantly higher TG and TC contents,higher expression levels of SREBP1(sterol regulatory element-binding protein 1),FAS(fatty acid synthase),and ACC1(acetyl-CoA carboxylase 1),more intracellular lipid aggregation,but lower viability,p-JAK2/JAK2 and p-STAT3/STAT3(all P＜0.05).Compared with those induced with high glucose,primary mouse liver cells induced with low-dose or high-dose STA had significantly lower TG and TC contents,lower expression levels of SREBP 1,FAS and ACC1,less intracellular lipid aggregation,but higher viability,p-JAK2/JAK2 and p-STAT3/STAT3(all P＜0.05).Application of the JAK2 inhibitor AG490 significantly reversed the role of high-dose STA in mediating cell viability and lipid metabolism(P＜0.05).Conclusion STA can inhibit high-glucose-induced lipid metabolism abnormalities in liver cells by activating the JAK2/STAT3 signaling pathway.