Green tea (-)-epigallocatechin gallate inhibits IGF-I and IGF-IIstimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor, but not AMP-activated protein kinase pathway

• Published in: Molecular nutrition & food research Vol. 56; no. 4; pp. 580 - 592
• Main Authors: Ku, Hui-Chen, Liu, Hang-Seng, Hung, Pei-Fang, Chen, Chia-Lin, Liu, Hsien-Chun, Chang, Hsin-Huei, Tsuei, Yi-Wei, Shih, Li-Jane, Lin, Ching-Ling, Lin, Chih-Ming, Kao, Yung-Hsi
• Format: Journal Article
• Language: English
• Published: Blackwell Publishing Ltd 01.04.2012
• Subjects: Epigallocatechin gallate / Green tea / Insulin-like growth factor / Laminin receptor / Preadipocyte
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201100438

Scope This study investigated the pathways involved in epigallocatechin gallate (EGCG) modulation of insulin‐like growth factor (IGF)‐I‐stimulated and IGF‐II‐stimulated mitogenesis in 3T3‐L1 preadipocytes. Methods and results We found that this process was dose and time dependent, and caused by suppression of IGF‐I‐stimulated and IGF‐II‐stimulated phosphorylation of p66Shc and mitogen‐activated protein kinase (MAPK) pathway proteins, including MEK1 kinase (RAF1), extracellular signal‐regulated protein kinase (ERK) kinase (MEK1), and ERK 1 and ERK 2 (ERK1/2), but not phospho‐Jun‐N‐terminal kinase, protein kinase B, p52Shc, or p46Shc. Furthermore, EGCGinhibited the IGF‐I‐stimulated phosphorylation of the IGF‐I receptor‐beta (IGF‐IR β), the association of IGF‐IRwith the p66Shc protein, and the IGF‐II‐stimulated associations of the IGF‐IIreceptor with Gαi‐2 and p66Shc proteins, suggesting that EGCGselectively affects particular types of Shc and MAPKfamily members. Pretreatment with antiserum against the EGCGreceptor (also known as the 67‐kDa laminin receptor; 67LR), but not with an adenosine monophosphate (AMP)‐activated protein kinase (AMPK) inhibitor, prevented the inhibitory actions of EGCGon IGF‐I‐ and IGF‐II‐stimulated ERK1/2 phosphorylation and subsequent preadipocyte proliferation. Conclusion The results of this study suggest that EGCGmediates anti‐IGF‐I and anti‐IGF‐IIsignals in preadipocyte mitogenesis via the 67LR but not the AMPKpathway.