US EPA

3418572 

Journal Article 

Endogenous sulfur dioxide is a novel adipocyte-derived inflammatory inhibitor 

Zhang, H; Huang, Y; Bu, D; Chen, S; Tang, C; Wang, G; Du, J; Jin, H 

2016 

1 

Scientific Reports
EISSN: 2045-2322 

6 

27026 

English 

27246393 

10.1038/srep27026 

WOS:000376866300001 

http://://WOS:000376866300001
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The present study was designed to determine whether sulfur dioxide (SO2) could be endogenously produced in adipocyte and served as a novel adipocyte-derived inflammatory inhibitor. SO2 was detected in adipose tissue using high-performance liquid chromatography with fluorescence detection. SO2 synthase aspartate aminotransferase (AAT1 and AAT2) mRNA and protein expressions in adipose tissues were measured. For in vitro study, 3T3-L1 adipocytes were cultured, infected with adenovirus carrying AAT1 gene or lentivirus carrying shRNA to AAT1, and then treated with tumor necrosis factor-α (TNF-α). We found that endogenous SO2/AAT pathway existed in adipose tissues including perivascular, perirenal, epididymal, subcutaneous and brown adipose tissue. AAT1 overexpression significantly increased SO2 production and inhibited TNF-α-induced inflammatory factors, monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) secretion from 3T3-L1 adipocytes. By contrast, AAT1 knockdown decreased SO2 production and exacerbated TNF-α-stimulated MCP-1 and IL-8 secretion. Mechanistically, AAT1 overexpression attenuated TNF-α-induced IκBα phosphorylation and degradation, and nuclear factor-κB (NF-κB) p65 phosphorylation, while AAT1 knockdown aggravated TNF-α-activated NF-κB pathway, which was blocked by SO2. NF-κB inhibitors, PDTC or Bay 11-7082, abolished excessive p65 phosphorylation and adipocyte inflammation induced by AAT1 knockdown. This is the first report to suggest that endogenous SO2 is a novel adipocyte-derived inflammatory inhibitor.