| The chronic low-grade inflammation of adipose tissue,which primarily mediates by adipose tissue macrophages(ATMs),is the key pathogenic link between obesity and metabolic disorders.Oleanolic acid(OA)is a natural triterpenoid possessing anti-diabetic and anti-inflammation effect.This study investigated the mechanism of OA on adipose tissue inflammation in obesity for the first time.C57BL/6J mice were fed with high-fat diet(HFD)for 12 weeks,then daily intragastric administrated with vehicle,25mg/kg OA and 50mg/kg OA for 4 weeks.Comparing with vehicle,OA improved insulin resistance and adipose tissue hypertrophy.Immunofluorescence and flow cytometry demonstrated that ATM infiltration,M1 proportion,M1/M2 ratio were down-regulated by OA.In RAW264.7 treated with IFN-γ/LPS and epidydimal white adipose tissue(e WAT)of obese mice,qPCR results indicated that pro-inflammatory markers were significantly down-regulated,furthermore,it was found that OA may inhibit activation of mitogen-activated protein kinase(MAPK)signaling and NLRP3 inflammasome through reducing voltage dependent anion channels(VDAC)expression and reactive oxygen species(ROS)production.These findings provide at least a partial mechanism for OA in the alleviation of HFD-induced obesity inflammatory response,which contributes to an improved obesity-associated metabolic status. |
