Polyphenols Attenuate Inflammatory Response Via Modulating the Crosstalk Between Macrophages and Adipocytes.

Obesity is characterized as a chronic state of low-grade inflammation with progressive immune cell infiltration into adipose tissue. Adipose tissue macrophages play a critical role in the establishment of chronic inflammatory states and metabolic dysfunctions. (.) and extract polyphenols exhibit anti-carcinogenesis, anti-inflammatory, and anti-oxidant activities. However, the action of polyphenols in obesity-related inflammation has not been reported. The aim of this study was to explore the anti-inflammatory action of polyphenols from extract (ISE) in macrophages and the interaction between macrophages and adipocytes. RAW264.7 macrophages were stimulated with LPS or conditioned medium of hypertrophied 3T3-L1 adipocytes or cocultured with differentiated adipocytes in the presence of different doses of ISE. The inflammatory cytokines were evaluated by ELISA, the MAPK, NF-κB, and IL-6/STAT3 signals were determined by immunoblotting, and the migrated function of macrophages was determined by migration assay. ISE suppressed the inflammatory mediators including NO, TNF-α, IL-6, and MCP-1 induced by either LPS or conditioned medium derived from 3T3-L1 adipocytes. ISE also decreased the production of these inflammatory mediators in cocultures of 3T3-L1 adipocytes and RAW264.7 macrophages. Furthermore, ISE blocked RAW264.7 macrophages migration toward 3T3-L1 adipocytes in cocultures. Finally, this effect of ISE might be mediated via inhibiting ERK, p38, and STAT3 activation. Our findings indicate the possibility that ISE suppresses the interaction between macrophages and adipocytes, attenuates chronic inflammation in adipose tissue and improves obesity-related insulin resistance and complication, suggesting that ISE might be a valuable medicinal food effective in improving insulin resistance and metabolic syndrome.