Blockade of visfatin induction by oleanolic acid via disturbing IL-6-TRAF6-NF-κB signaling of adipocytes.
Oleanolic acid is a pentacyclic triterpenoid naturally present in foods and medicinal plants with anticancer, antioxidant, and antiaging properties. The current study elucidated that oleanolic acid inhibited the production of insulin-mimetic and inflammatory adipokine of visfatin during adipogenic differentiation of 3T3-L1 adipocytes. Adipocytes were cultured in an adipogenic media with and without 1-25 µM oleanolic acid up to 8 days for differentiation. The cellular expression and secretion of visfatin was markedly enhanced in differentiating adipocytes, which was dose-dependently attenuated by 1-25 µM oleanolic acid. Secretion of interleukin (IL)-6 and macrophage inflammatory protein (MIP)-2 was highly elevated during differentiation, which was much earlier than visfatin production of adipocytes. The visfatin production was secondary to inflammatory IL-6 and MIP-2. This study further elucidated that nuclear factor-κB (NF-κB) signaling was responsible for cellular production of visfatin. NF-κB was activated by translocating into the nucleus with increased phosphorylation of inhibitory κB (IκB), which was disturbed by oleanolic acid. Cellular expression of tumor necrosis factor receptor associated factor 6 (TRAF6), a NF-κB upstream, was upregulated in parallel with transactivation with NF-κB. The TRAF6 induction required the auto-stimulation of inflammatory IL-6 and MIP-2. These results demonstrate that oleanolic acid inhibited visfatin and its inflammatory response during adipocyte differentiation through blocking IL-6-TRAF6-NF-κB signaling. Therefore, oleanolic acid may be a potent therapeutic agent targeting against adipogenesis and visfatin-linked inflammation.
Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea.
Hyun-Sung
HS
Kim
Seon-Young
SY
Han
Hye-Young
HY
Sung
Sin-Hye
SH
Park
Min-Kyung
MK
Kang
Seoung-Jun
SJ
Han
Young-Hee
YH
Kang
D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D054426:Chemokine CXCL2 / Q000096:biosynthesis / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009828:Oleanolic Acid / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*
D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D015850:Interleukin-6; D016328:NF-kappa B; D048029:TNF Receptor-Associated Factor 6; C577686:interleukin-6, mouse; D009828:Oleanolic Acid; D054409:Nicotinamide Phosphoribosyltransferase; D051550:I-kappa B Kinase
Adipocyte differentiation; TRAF6; nuclear factor-κB; obesity; oleanolic acid; visfatin