Polyinosinic-polycytidylic acid inhibits the differentiation of mouse preadipocytes through pattern recognition receptor-mediated secretion of tumor necrosis factor-α.
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.
Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan Province, China.|Research Center for Immunology, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan Province, China.
Lili
L
Yu
Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan Province, China.|Research Center for Immunology, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan Province, China.
Guoyan
G
Liu
Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan Province, China.|Research Center for Immunology, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan Province, China.
Can
C
Yang
Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan Province, China.|Research Center for Immunology, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan Province, China.
Xiangfeng
X
Song
Research Center for Immunology, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan Province, China.
Hui
H
Wang
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002469:Cell Separation; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011070:Poly I-C / Q000494:pharmacology*; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D013997:Time Factors; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D051192:Receptors, Pattern Recognition; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; D011070:Poly I-C