Isoliquiritigenin Attenuates Adipose Tissue Inflammation in vitro and Adipose Tissue Fibrosis through Inhibition of Innate Immune Responses in Mice.

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.

• Authors: Yasuharu Watanabe, Yoshinori Nagai, Hiroe Honda, Naoki Okamoto, Seiji Yamamoto, Takeru Hamashima, Yoko Ishii, Miyako Tanaka, Takayoshi Suganami, Masakiyo Sasahara, Kensuke Miyake, Kiyoshi Takatsu
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 23097 (Mar 15 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 26975571 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Chalcones
• Inflammasomes
• Lipopolysaccharides
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• isoliquiritigenin

Topics

• Adipocytes (drug effects, immunology, pathology)
• Adipose Tissue, White (drug effects, immunology, pathology)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Cell Differentiation
• Chalcones (pharmacology, therapeutic use)
• Coculture Techniques
• Diet, High-Fat
• Fibrosis (prevention & control)
• Immunity, Innate (drug effects)
• Inflammasomes (drug effects, immunology)
• Inflammation (immunology, pathology, prevention & control)
• Interferon-gamma (pharmacology)
• Lipopolysaccharides (pharmacology)
• Macrophages (drug effects, immunology, pathology)
• Male
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Paracrine Communication
• Tumor Necrosis Factor-alpha (metabolism)