title: Inhibition of adipocyte inflammation and macrophage chemotaxis by butein.
abstract: Adipose tissue inflammation has been proposed as a therapeutic target for the treatment of obesity and metabolic disorders such as insulin resistance and type 2 diabetes. Butein, a polyphenol of vegetal origin, exhibits anti-inflammatory effects in macrophages but it was not reported whether butein prevents adipocyte inflammation. Here, we investigated the effects of butein on adipocyte inflammation in 3T3-L1 cells and performed functional macrophage migration assays. Butein opposed the stimulation of inducible nitric oxide synthase (iNOS) protein expression and of nitric oxide production by simultaneous treatment of adipocytes with tumor necrosis factor alpha (TNFα), lipopolysaccharide (LPS), and interferon gamma (TLI). In addition, butein inhibited mRNA expression of pro-inflammatory genes and chemokines in adipocytes stimulated with TLI or conditioned medium from RAW 264.7 macrophages treated with LPS. These effects were associated with suppression of inhibitor of kappa B alpha degradation induced by TNFα and with nuclear factor-kappa B (NF-κB) p65 phosphorylation and acetylation. Moreover, butein prevented phosphorylation of extracellular signal-regulated kinases, c-Jun N-terminal kinase, and the mitogen-activated protein kinase (MAPK) p38. These results suggest that butein suppresses adipocyte inflammation by inhibiting NF-κB/MAPK-dependent transcriptional activity. Furthermore, conditioned media from adipocytes stimulated macrophage chemotaxis, whereas media from adipocytes treated with butein blocked macrophage migration, an effect that was consistent with suppression of MCP-1 secretion by adipocytes treated with butein. In addition, macrophages treated with butein exhibited a reduced ability to migrate toward adipocyte CM. In conclusion, butein may represent a therapeutic agent to prevent adipose tissue inflammation and the obesity-linked insulin resistance.
authors.affiliation: College of Pharmacy, Woosuk University, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Woosuk University, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Youngyi
authors.initials: Y
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Woosuk University, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Jae Soon
authors.initials: JS
authors.lastname: Eun
authors.affiliation: College of Pharmacy, Woosuk University, Wanju-gun, Jeollabuk-do, Republic of Korea. Electronic address: ejbae@woosuk.ac.kr.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Bae
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D047188:Chalcones / Q000494:pharmacology* / Q000627:therapeutic use; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D047188:Chalcones; D018925:Chemokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C040918:butein; D052247:Nitric Oxide Synthase Type II
keywords: Adipocytes; Butein; Butein (PubChem CID: 5281222); Chemokines; IFN gamma (PubChem SID:57288557); Inflammation; LPS (PubChem CID: 11970143); Macrophage chemotaxis; TNF alpha (PubChem SID:57288613)