The Radioprotective 105/MD-1 Complex Contributes to Diet-Induced Obesity and Adipose Tissue Inflammation

Watanabe, Yoshifumi; Nakamura, Tomoya; Ishikawa, Sho; Fujisaka, Shiho; Usui, Isao; Tsuneyama, Koichi; Ichihara, Yasuko; Wada, Tsutomu; Hirata, Yoichiro; Suganami, Takayoshi; Ishikawa, Hirofumi; Akira, Shizuo; Miyake, Kensuke; Kanayama, Hiro Omi; Shimabukuro, Michio; Sata, Masataka; Sasaoka, Toshiyasu; Ogawa, Yoshihiro; Tobe, Kazuyuki; Takatsu, Kiyoshi; Nagai, Yoshinori

doi:10.2337/db11-1182

Cited by 43 publications

(58 citation statements)

References 39 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, HFD-induced obesity, adipose tissue inflammation, and insulin resistance are severely attenuated in RP105 KO mice compared with wildtype (WT) and TLR4 KO mice. In contrast to TLR4, RP105 is not activated by palmitic acid [32]. Our results suggest that ligands and signaling pathways involved in RP105-mediated adipose tissue inflammation do not completely overlap with those utilized by TLR4.…”

Section: Toll-like Receptorsmentioning

confidence: 53%

“…We have showed that RP105 is indispensable for TLR4-dependent plasma cell differentiation and IgM production in MZ B cells [36]. Additionally, M1 macrophages of murine epididymal white adipose tissue (eWAT) highly express RP105 [32]. This expression is markedly increased by HFD supplementation [32].…”

Section: Toll-like Receptorsmentioning

confidence: 89%

“…Additionally, M1 macrophages of murine epididymal white adipose tissue (eWAT) highly express RP105 [32]. This expression is markedly increased by HFD supplementation [32]. Furthermore, HFD-induced obesity, adipose tissue inflammation, and insulin resistance are severely attenuated in RP105 KO mice compared with wildtype (WT) and TLR4 KO mice.…”

Section: Toll-like Receptorsmentioning

confidence: 91%

“…We previously demonstrated that the development of obesity-related inflammation required radioprotective 105 (RP105) rather than TLR4 [32]. RP105 was identified as a first mammalian homologue of Drosophila toll that expressed on B cells [33] and suggested to be involved in LPS-induced B-cell responses.…”

Section: Toll-like Receptorsmentioning

confidence: 99%

See 3 more Smart Citations

Isoliquiritigenin: A Unique Component That Attenuates Adipose Tissue Inflammation and Fibrosis by Targeting the Innate Immune Sensors

Nagai¹,

Watanabe²,

Honda³

et al. 2017

Biological Activities and Action Mechanisms of Licorice Ingredients

Self Cite

View full text Add to dashboard Cite

Recent studies have suggested that pattern recognition receptors, including inflammasomes and TLRs, in the innate immune system recognize various kinds of endogenous ligands and have critical roles in initiating or promoting obesity-associated chronic inflammation. These findings have provided new therapeutic strategies based on regulation of the innate immune system. With the rapid advancement of novel technologies and the increased research on natural products, many new plant-derived extracts and active compounds have been identified to exhibit anti-inflammatory effects. Isoliquiritigenin (ILG) is a flavonoid derived from Glycyrrhiza uralensis with a chalcone structure. We have reported that ILG inhibits NLRP3 inflammasome activation resulting in the improvement of diet-induced adipose tissue inflammation and insulin resistance. Furthermore, we have also demonstrated that ILG improves diet-induced fibrosis in adipose tissue by inhibiting TLR4-and Mincle-induced expression of fibrosis-related genes in obese adipose tissue and macrophages. Thus, ILG can suppress two important dysfunctions of obesity, adipose tissue inflammation and fibrosis by targeting innate immune sensors. Here we overview ILG as a potential therapeutic agent for the treatment of obesity-associated diseases. We also summarize anti-inflammatory actions of other constituents of licorice.

show abstract

Section: Toll-like Receptorsmentioning

confidence: 53%

Section: Toll-like Receptorsmentioning

confidence: 89%

Section: Toll-like Receptorsmentioning

confidence: 91%

Section: Toll-like Receptorsmentioning

confidence: 99%

See 2 more Smart Citations

Isoliquiritigenin: A Unique Component That Attenuates Adipose Tissue Inflammation and Fibrosis by Targeting the Innate Immune Sensors

Nagai¹,

Watanabe²,

Honda³

et al. 2017

Biological Activities and Action Mechanisms of Licorice Ingredients

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, it was reported that the RP105-MD-1 complex, a homolog of TLR4-MD-2, was expressed in adipose tissue-associated macrophages and might receive endogenous ligands derived from adipocytes, leading to chronic inflammation (34). Thus, pattern-recognition receptors in innate immune systems certainly recognize noninfectious endogenous ligands and contribute to the pathogenesis of inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

TLR4–MD-2 complex is negatively regulated by an endogenous ligand, globotetraosylceramide

Kondo¹,

Ikeda

Tokuda³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Although endogenous ligands for Toll-like receptor (TLR)4-myeloid differentiation factor 2 (MD2) have not been well-understood, we here report that a globo-series glycosphingolipid, globotetraosylceramide (Gb4), attenuates the toxicity of lipopolysaccharides (LPSs) by binding to TLR4-MD-2. Because α1,4-galactosyltransferase (A4galt)-deficient mice lacking globo-series glycosphingolipids showed higher sensitivity to LPS than wild-type mice, we examined mechanisms by which globo-series glycosphingolipids attenuate LPS toxicity. Cultured endothelial cells lacking A4galt showed higher expression of LPS-inducible genes upon LPS treatment. In turn, introduction of A4galt cDNA resulted in the neo expression of Gb4, leading to the reduced expression of LPS-inducible genes. Exogenous Gb4 induced similar effects. As a mechanism for the suppressive effects of Gb4 on LPS signals, specific binding of Gb4 to the LPS receptor TLR4-MD-2 was demonstrated by coprecipitation of Gb4 with recombinant MD-2 and by native PAGE. A docking model also supported these data. Taken together with colocalization of TLR4-MD-2 with Gb4 in lipid rafts after LPS stimulation, it was suggested that Gb4 competes with LPS for binding to TLR4-MD-2. Finally, administration of Gb4 significantly protected mice from LPS-elicited mortality. These results suggest that Gb4 is an endogenous ligand for TLR4-MD-2 and is capable of attenuating LPS toxicity, indicating the possibility for its therapeutic application in endotoxin shock.innate immunity | sepsis

show abstract

Depot‐ and gender‐specific expression of NLRP3 inflammasome and toll‐like receptors in adipose tissue of cancer patients

et al. 2016

Self Cite

View full text Add to dashboard Cite

Gender difference in obesity-associated cardiovascular complication could be derived from divergent chronic inflammation. We evaluated depot- and gender-specific regulation of the innate immune system in human adipose tissues. Pair samples were obtained from subcutaneous (SAT) and visceral adipose tissue (VAT) during elective surgery (Male: 35; Female: 27). Expressions of pro- and anti-inflammatory adipocytokines were evaluated by semi-quantitative qPCR. Adipose cell-size distribution was obtained from tissue samples fixed in osmium tetroxide and analyzed by Beckman Coulter Multisizer. Levels of adiponectin were higher in SAT and VAT of female than those of male (P < 0.001 and P = 0.011, respectively). NLRP3, IL1β-IL18, TLR2 were comparable in SAT and VAT between genders. However, TLR4 and TLR9 were increased in female SAT and VAT and HMGB1 in female VAT. Levels of adiponectin were not correlated with mean diameter of adipocyte (φ, μm) in SAT and VAT of male, but negatively well correlated in those of female (r = -0.392 and r = -0.616). Such negative correlations were also observed between levels of TLR2, TLR4, and HMGB1 and φ in female. Levels of NLRP3 and IL1β were positively correlated with φ in male, but not in female. In conclusion, Innate signals were differentially expressed in male and female adipose tissues, suggesting that the depot- and gender-specific signals could be related to gender difference in chronic inflammation. © 2016 BioFactors, 42(4):397-406, 2016.

show abstract

The Radioprotective 105/MD-1 Complex Contributes to Diet-Induced Obesity and Adipose Tissue Inflammation

Cited by 43 publications

References 39 publications

Isoliquiritigenin: A Unique Component That Attenuates Adipose Tissue Inflammation and Fibrosis by Targeting the Innate Immune Sensors

Isoliquiritigenin: A Unique Component That Attenuates Adipose Tissue Inflammation and Fibrosis by Targeting the Innate Immune Sensors

TLR4–MD-2 complex is negatively regulated by an endogenous ligand, globotetraosylceramide

Depot‐ and gender‐specific expression of NLRP3 inflammasome and toll‐like receptors in adipose tissue of cancer patients

Contact Info

Product

Resources

About