title: Diosgenin attenuates inflammatory changes in the interaction between adipocytes and macrophages.
abstract: Obese adipose tissues are characterized by the enhanced infiltration of macrophages. It is considered that the paracrine loop involving monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and the free fatty acid between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes and insulin resistance in obese adipose tissues. Diosgenin, a saponin aglycon found in a variety of plants, has anti-inflammatory properties. In the present study, we examined the effect of diosgenin on the inflammatory changes in the interaction between adipocytes and macrophages. A coculture of 3T3-L1 adipocytes and RAW 264 macrophages markedly enhanced the production of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and nitric oxide compared with the sum of their single cultures; however, treatment with diosgenin inhibited the production of these proinflammatory mediators. Diosgenin also suppressed the inflammation in RAW 264 macrophages that was induced by the conditioned medium derived from 3T3-L1 adipocytes. Furthermore, diosgenin inhibited the conditioned medium-induced degradation of inhibitor kappaB and the phosphorylation of c-jun N-terminal kinase in macrophages. These results indicate that diosgenin exhibits anti-inflammatory properties in the interaction of adipocytes and macrophages by inhibiting the inflammatory signals in macrophages. Diosgenin may be useful for ameliorating the inflammatory changes in obese adipose tissues.
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Hirai
authors.forename: Taku
authors.initials: T
authors.lastname: Uemura
authors.forename: Noriko
authors.initials: N
authors.lastname: Mizoguchi
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Keiko
authors.initials: K
authors.lastname: Taketani
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakano
authors.forename: Shohei
authors.initials: S
authors.lastname: Hoshino
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tsuge
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Narukami
authors.forename: Rina
authors.initials: R
authors.lastname: Yu
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D018920:Coculture Techniques; D004144:Diosgenin / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000502:physiology; D020672:I-kappa B Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D051197:Toll-Like Receptor 4 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D005230:Fatty Acids, Nonesterified; D020672:I-kappa B Proteins; C000606205:Nfkbia protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D048031:JNK Mitogen-Activated Protein Kinases; D004144:Diosgenin