Oleanolic acid reduces markers of differentiation in 3T3-L1 adipocytes

Oleanolic acid is a triterpenoid compound that is widely present in vegetables, medicinal herbs, and other plants and has potent antioxidant and antiinflammatory properties. However, the potential of oleanolic acid to offset obesity is not clear. This study tested the hypothesis that oleanolic acid suppresses the differentiation of 3T3-L1 adipocytes by downregulating cellular induction of peroxisome proliferators-activated receptor gamma (PPAR gamma) and cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT) enhancer binding protein alpha (C/EBP alpha). The 3T3-L1 adipocytes were cultured and differentiated in Dulbecco modified Eagle medium containing 10% fetal bovine serum for 6 to 8 days in the absence and presence of 1 to 25 mu mol/L oleanolic acid according to differentiating protocols. Nontoxic oleanolic acid, at 25 mu mol/L or less, dose-dependently attenuated lipid accumulation in differentiated adipocytes as evidenced by Oil Red O staining. Western blot analysis showed that the induction of PPAR gamma and C/EBP alpha was markedly attenuated in differentiated and oleanolic acid-treated adipocytes at their transcriptional messenger RNA levels. Furthermore, this study examined whether oleanolic acid dampened the induction of visfatin, a proinflammatory and visceral fat-specific adipokine expressed in adipocytes. Visfatin expression was inhibited in differentiated adipocytes exposed to a PPAR gamma inhibitor GW9662. In addition, the visfatin production was significantly repressed in 25 mu mol/L oleanolic acid-treated adipocytes, possibly through blocking PPAR gamma activation. These results demonstrate that oleanolic acid may be a promising agent to disturb adipocyte differentiation and suppress obesity-associated inflammation. (C) 2010 Elsevier Inc. All rights reserved.