| RRC ID |
37880
|
| 著者 |
Watanabe Y, Nagai Y, Honda H, Okamoto N, Yamamoto S, Hamashima T, Ishii Y, Tanaka M, Suganami T, Sasahara M, Miyake K, Takatsu K.
|
| タイトル |
Isoliquiritigenin Attenuates Adipose Tissue Inflammation in vitro and Adipose Tissue Fibrosis through Inhibition of Innate Immune Responses in Mice.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Isoliquiritigenin (ILG) is a flavonoid derived from Glycyrrhiza uralensis and potently suppresses NLRP3 inflammasome activation resulting in the improvement of diet-induced adipose tissue inflammation. However, whether ILG affects other pathways besides the inflammasome in adipose tissue inflammation is unknown. We here show that ILG suppresses adipose tissue inflammation by affecting the paracrine loop containing saturated fatty acids and TNF-α by using a co-culture composed of adipocytes and macrophages. ILG suppressed inflammatory changes induced by the co-culture through inhibition of NF-κB activation. This effect was independent of either inhibition of inflammasome activation or activation of peroxisome proliferator-activated receptor-γ. Moreover, ILG suppressed TNF-α-induced activation of adipocytes, coincident with inhibition of IκBα phosphorylation. Additionally, TNF-α-mediated inhibition of Akt phosphorylation under insulin signaling was alleviated by ILG in adipocytes. ILG suppressed palmitic acid-induced activation of macrophages, with decreasing the level of phosphorylated Jnk expression. Intriguingly, ILG improved high fat diet-induced fibrosis in adipose tissue in vivo. Finally, ILG inhibited TLR4- or Mincle-stimulated expression of fibrosis-related genes in stromal vascular fraction from obese adipose tissue and macrophages in vitro. Thus, ILG can suppress adipose tissue inflammation by both inflammasome-dependent and -independent manners and attenuate adipose tissue fibrosis by targeting innate immune sensors.
|
| 巻・号 |
6
|
| ページ |
23097
|
| 公開日 |
2016-3-15
|
| DOI |
10.1038/srep23097
|
| PII |
srep23097
|
| PMID |
26975571
|
| PMC |
PMC4791553
|
| MeSH |
Adipocytes / drug effects*
Adipocytes / immunology
Adipocytes / pathology
Adipose Tissue, White / drug effects*
Adipose Tissue, White / immunology
Adipose Tissue, White / pathology
Animals
Anti-Inflammatory Agents / pharmacology*
Anti-Inflammatory Agents / therapeutic use
Cell Differentiation
Chalcones / pharmacology*
Chalcones / therapeutic use
Coculture Techniques
Diet, High-Fat
Fibrosis / prevention & control
Immunity, Innate / drug effects
Inflammasomes / drug effects
Inflammasomes / immunology
Inflammation / immunology
Inflammation / pathology
Inflammation / prevention & control
Interferon-gamma / pharmacology
Lipopolysaccharides / pharmacology
Macrophages / drug effects
Macrophages / immunology
Macrophages / pathology
Male
Mice, Inbred C57BL
NF-kappa B / metabolism
Paracrine Communication
Tumor Necrosis Factor-alpha / metabolism
|
| IF |
3.998
|
| 引用数 |
36
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
