Theaflavin-3, 3′-digallate, a black tea polyphenol, attenuates adipocyte-activated inflammatory response of macrophage associated with the switch of M1/M2-like phenotype

The paracrine-loop of hypertrophic adipocytes and macrophages in adipose tissue mediates chronic inflammation state (metaflammation) that closely links to disease development in obesity. We investigated the metaflammation-preventing effect of theaflavin-3, 3′-digallate (TF3) in a transwell-co-culture system comprising 3T3-L1 adipocytes and Raw264.7 macrophages. TF3 suppressed the induction of pro-inflammatory mediators, NO, TNF-α, IL-6, IL-1β, and MCP-1, while it enhanced anti-inflammatory cytokine, IL-10, in the co-culture. Inflammatory change of co-cultured macrophages was associated with the switch of M2 characteristic gene expression profile (CD206, CD163 and arginase-1) to M1 phenotype hallmarks (CD11c, CCR7, and CD86). TF3 promoted the shift of M1-like CD206−CD11c+ inflammatory phenotype of macrophage toward less inflammatory CD206+CD11c+ M2-like cells. On the other hand, TF3 enhanced the expression of anti-inflammatory adiponectin and reduced the release of free fatty acids, TNF-α, and IL-6 by adipocytes through AMPK-dependent pathway. Thus, TF3 is a loop-breaking cue that prevents inflammatory response ignited by adipocyte-macrophage interaction.