title: Oleanolic acid suppresses resistin induction in adipocytes by modulating Tyk-STAT signaling.
abstract: Oleanolic acid, a naturally occurring triterpenoid widely distributed in foods and medicinal plants, has anticancer, antioxidant, and antiaging properties. We hypothesized that oleanolic acid would suppress the production of the inflammatory adipokine resistin during adipogenic differentiation of 3T3-L1 adipocytes. 3T3-L1 adipocytes were cultured in adipogenic media with and without 1 to 25 μM oleanolic acid for up to 8 days to stimulate adipocyte differentiation. Adipocyte production of resistin was markedly enhanced during differentiation and was dose dependently attenuated by 1 to 25 μM oleanolic acid. This study further investigated whether Tyk2-Stat1/3 signaling was responsible for cellular production of resistin. Signal transducer and activator of transcription factor (STAT) 1 and STAT3 were activated during differentiation in a disparate temporal fashion; STAT1 was maximally phosphorylated on day 5 after initiating differentiation, whereas STAT3 was rapidly activated within 1 day of differentiation. When oleanolic acid was supplied to differentiating adipocytes, STAT1 and STAT3 phosphorylation was substantially suppressed. Upstream Tyk2 was rapidly activated in a manner similar to STAT3 and reactivated on days 3 to 5 after initiating differentiation, which was attenuated by incubating adipocytes with oleanolic acid. In addition, cellular expression of suppressor of cytokine signaling 3 (SOCS3), which inhibits Tyk2 activity, was markedly promoted from day 5 of adipocyte differentiation. Oleanolic acid attenuated SOCS3 expression, which was highly enhanced during the late phase of differentiation. Taken together, oleanolic acid suppressed adipocyte differentiation-associated resistin and adipogenesis production by disturbing the Tyk2-STAT1/3 signaling pathway and promoting SOCS3 expression. Therefore, oleanolic acid may be a possible bioactive agent that blunts adipogenesis and adipokine inflammation.
authors: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Republic of Korea.
authors: Hyun-Sung
authors: HS
authors: Kim
authors: Hye-Young
authors: HY
authors: Sung
authors: Min Soo
authors: MS
authors: Kim
authors: Jung-Lye
authors: JL
authors: Kim
authors: Min-Kyung
authors: MK
authors: Kang
authors: Ju-Hyun
authors: JH
authors: Gong
authors: Hyoung-Sook
authors: HS
authors: Park
authors: Young-Hee
authors: YH
authors: Kang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D051379:Mice; D009828:Oleanolic Acid / Q000494:pharmacology*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D052243:Resistin / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D053634:TYK2 Kinase / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D052243:Resistin; D050791:STAT Transcription Factors; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D009828:Oleanolic Acid; D053634:TYK2 Kinase; C499356:Tyk2 protein, mouse