Diosgenin attenuates inflammatory changes in the interaction between adipocytes and macrophages.
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.
Hirai
Shizuka
S
Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
Uemura
Taku
T
Mizoguchi
Noriko
N
Lee
Joo-Young
JY
Taketani
Keiko
K
Nakano
Yuki
Y
Hoshino
Shohei
S
Tsuge
Nobuaki
N
Narukami
Toshihiko
T
Yu
Rina
R
Takahashi
Nobuyuki
N
Kawada
Teruo
T
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
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