Myeloid Cell-Specific Knockout of 67-kDa Laminin Receptor Abolishes the Antifibrotic and Antiobesity Effects of Green Tea Polyphenol EGCG

Green tea, particularly its active ingredient (-)-epigallocatechin-3-O-gallate (EGCG), reduces the risk of cancer, liver disease and obesity, however, the precise mechanisms underlying these effects remain unclear. Herein, we examined the role of the myeloid cell 67-kDa laminin receptor (67LR) in mediating its physiological effects and demonstrated that the therapeutic effects of EGCG on liver fibrosis and obesity were attenuated in myeloid cell-specific 67LR knockout (67LR^ΔLysM) mice. EGCG treatment ameliorated liver fibrosis in the control 67LR^fl/fl male mice but not in the 67LR^ΔLysM male mice. Next-generation sequencing revealed that EGCG regulates miRNA expression in macrophages through the 67LR. Our results elucidated the anti-inflammatory mechanisms of EGCG through a transcriptomic analysis of adipose tissues. In addition, EGCG supplementation suppressed macrophage recruitment, glucose intolerance, and adipose inflammation in the control 67LR^fl/fl male mice, but not in the 67LR^ΔLysM male mice. In conclusion, EGCG exerts antifibrotic and antiobesity effects mediated by the 67LR.