The Radioprotective 105/MD-1 Complex Contributes to Diet-induced Obesity and Adipose Tissue Inflammation (172.23)

• Published in: The Journal of Immunology Vol. 188; no. 1_Supplement; p. 172.23
• Main Authors: Watanabe, Yasuharu, Nagai, Yoshinori, Nakamura, Tomoya, Akira, Shizuo, Miyake, Kensuke, Takatsu, Kiyoshi
• Format: Journal Article
• Language: English; Japanese
• Published: The American Association of Immunologists 01.05.2012
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.188.supp.172.23

Accumulating evidence suggest that innate immunity is associated with obesity-induced chronic inflammation and metabolic disorders. For example, the TLR4/MD-2 complex recognizes free fatty acids (FAAs) derived from adipose tissue and promotes adipose tissue inflammation and insulin resistance. The RP105/MD-1 complex is a homolog of the TLR4/MD-2 complex. However, the roles of RP105/MD-1 complex in adipose tissue inflammation have remained elusive. We now report that the RP105/MD-1 complex contributes to high-fat diet (HFD)-induced obesity, adipose tissue inflammation, and insulin resistance independent of TLR4 signaling. RP105 mRNA expression is dramatically increased by HFD in stromal vascular fraction of epididymal white adipose tissue (eWAT) in wild-type (WT) mice. In human, RP105 mRNA expression is also increased in the visceral adipose tissue of obese subjects. The RP105/MD-1 complex is expressed by most adipose tissue macrophages (ATMs). HFD increases RP105/MD-1 expression on the M1 ATMs in eWAT. Increased RP105 and MD-1 mRNA expression in macrophages is induced by co-culture with 3T3L-1 adipocytes. RP105 KO and MD-1 KO mice have less HFD-induced adipose tissue inflammation, hepatic steatosis and insulin resistance compared to these in WT and TLR4 KO mice. Finally, the saturated FAAs palmitic and stearic acids activate TLR4/MD-2 but not RP105/MD-1. Thus, the RP105/MD-1 complex is a major mediator of adipose tissue inflammation independent of TLR4 signaling.