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Polyinosinic‐polycytidylic acid inhibits the differentiation of mouse preadipocytes through pattern recognition receptor‐mediated secretion of tumor necrosis factor‐α
Author(s) -
Yu Lili,
Liu Guoyan,
Yang Can,
Song Xiangfeng,
Wang Hui
Publication year - 2016
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2016.57
Subject(s) - tlr3 , adipogenesis , biology , retinoic acid , tumor necrosis factor alpha , cellular differentiation , microbiology and biotechnology , receptor , transfection , adipocyte , endocrinology , adipose tissue , chemistry , medicine , innate immune system , toll like receptor , biochemistry , gene
Viral infections can disturb the functions of adipose tissues and thus result in metabolic diseases. Polyinosinic‐polycytidylic acid (poly(I:C)), a synthetic analog of viral double‐stranded RNA, induces innate antiviral responses by mimicking viral infection through the activation of pattern recognition receptors (PRRs) such as Toll‐like receptor 3 (TLR3), retinoic acid‐inducible gene I (RIG‐I) and melanoma differentiation‐associated gene 5 (MDA5). Poly(I:C) also inhibits the differentiation of mouse preadipocytes but the mechanism underlying this process remains unclear. In this study, poly(I:C) inhibited preadipocyte differentiation in a dose‐dependent manner, but not in a time‐dependent manner. Endogenously transfected poly(I:C) severely impaired the adipogenesis of preadipocytes compared with exogenously added poly(I:C). Low concentration of tumor necrosis factor‐α (TNF‐α) could effectively inhibit the preadipocyte differentiation. The effect of exogenously added poly(I:C) on inhibition of differentiation was significantly diminished in the preadipocytes of TLR3 knockout mice. By contrast, endogenously transfected poly(I:C) still inhibited the differentiation of TLR3 ‐deficient preadipocytes. Hence, MDA5/RIG‐I signaling was involved in the poly(I:C)‐induced inhibition of preadipocyte differentiation. The effect of poly(I:C) stimulation, either through endogenous transfection or exogenous addition, on inhibition of differentiation was significantly diminished in the preadipocytes of TNF‐α knockout mice. These results confirmed the evidence that poly(I:C) inhibited the differentiation of mouse preadipocytes through PRR‐mediated secretion of TNF‐α.