Green tea (−)-epigallocatechin gallate inhibits insulin stimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor pathway

Abstract

Insulin and (-)-epigallocatechin gallate (EGCG) have been reported to regulate fat cell mitogenesis and adipogenesis, respectively. This study investigated the pathways involved in EGCG modulation of insulin-stimulated mitogenesis in 3T3-L1 preadipocytes. EGCG inhibited insulin stimulation of preadipocyte proliferation in a dose- and time-dependent manner. EGCG also suppressed insulin-stimulated phosphorylation of the insulin receptor-beta, insulin receptor (IR) substrates 1 and 2 (IRS1 and IRS2), and mitogen-activated protein kinase pathway proteins, RAF1, MEK1/2, and ERK1/2, but not JNK. Furthermore, EGCG inhibited the association of IR with the IRS1 and IRS2 proteins, but not with the IRS4 protein. These data suggest that EGCG selectively affects particular types of IRS and MAPK family members. Generally, EGCG was more effective than epicatechin, epicatechin gallate, and epigallocatechin in modulating insulin-stimulated mitogenic signaling. We identified the EGCG receptor [also known as the 67-kDa laminin receptor (67LR)] in fat cells and found that its expression was sensitive to growth phase, tissue type, and differentiation state. Pretreatment of preadipocytes with 67LR antiserum prevented the effects of EGCG on insulin-stimulated phosphorylation of IRS2, RAF1, and ERK1/2 and insulin-stimulated preadipocyte proliferation (cell number and bromodeoxyuridine incorporation). Moreover, EGCG tended to increase insulin-stimulated associations between the 67LR and IR, IRS1, IRS2, and IRS4 proteins. These data suggest that EGCG mediates anti-insulin signaling in preadipocyte mitogenesis via the 67LR pathway.

(−)-Epigallocatechin-3-gallate blocks 3T3-L1 adipose conversion by inhibition of cell proliferation and suppression of adipose phenotype expression

“…Previous studies reported that treatment of 3T3-L1 cells with EGCG leads to a reduction in cell number Ku et al, 2009;Wu et al, 2005). Consistently, our findings show that EGCG exerts a suppressive effect on the proliferative rate of cell cultures in a dose dependent manner.…”

Epigallocatechin-3-gallate prevents TNF-α-induced NF-κB activation thereby upregulating ABCA1 via the Nrf2/Keap1 pathway in macrophage foam cells

“…It is reported that a 67-kDa laminin receptor (67LR), as the cell surface EGCG receptor, may be involved in mediating these actions of EGCG (22)(23)(24)(25). Moreover, EGCG is also believed to exert an Epigallocatechin-3-gallate prevents TNF-α-induced NF-κB activation thereby upregulating ABCA1 via the Nrf2/Keap1 pathway in macrophage foam cells anti-atherosclerotic effect via anti-inflammatory and metabolic regulation activities (26,27).…”

TLR4 Signaling Inhibitory Pathway Induced by Green Tea Polyphenol Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor

“…Furthermore, this receptor has also been shown to be responsible for antiallergic effects of EGCG in basophils (26,27). In preadipocytes, EGCG has been reported to mediate anti-insulin signaling via the 67LR pathway (28). However, it is not clear whether EGCG action through 67LR involves the negative regulatory effect of EGCG for inflammatory responses.…”