A Triterpenoid Inhibited Hormone-Induced Adipocyte Differentiation and Alleviated Dexamethasone-Induced Insulin Resistance in 3T3-L1 adipocytes

摘要

6α-Hydroxylup-20(29)-en-3-on-28-oic acid (1), a natural triterpenoid, was found to possess the ability in a dose-dependent manner inhibiting hormone-induced adipocyte differentiation in 3T3-L1 preadipocytes, and restoring glucose consuming ability in dexamethasone (DXM)-induced insulin resistant 3T3-L1 adipocytes. Compound 1 was also found to ameliorate DXM-induced adipocyte dysfunction in lipolysis and adipokine secretion. Mechanistic studies revealed that 1 inhibited adipocyte differentiation in 3T3-L1 preadipocytes via down-regulating hormone-stimulated gene transcription of peroxisome proliferator-activated receptor γ and CCAAT-enhancer-binding protein alpha which are key factors in lipogenesis, and restored DXM-impaired glucose consuming ability in differentiated 3T3-L1 adipocytes via repairing insulin signaling pathway and activating down-stream signaling transduction by phosphorylation of signaling molecules PI3K/p85, Akt2 and AS160, thus leading to increased translocation of glucose transporter type 4 and transportation of glucose.Graphical Abstract