| dc.description.abstract | Green tea catechins (GTCs) and microRNA (miR) molecules have been reported to regulate development of obesity, respectively, as characterized by changes in the mitogenic and adipogenic processes of fat cells. No studies were found on the miR-mediated effects of GTC, particularly epigallocatechin gallate (EGCG), on fat cell growth. Using 3T3-L1 white preadipocytes, we found that EGCG upregulated 20 miR molecules (e.g., mmu-miR-1224-5p, mmu-miR-711, and mmu-miR-8108) and downregulated 20 miR molecules (e.g., mmu-miR-668-3p and mmu-miR-690). Further RT-qPCR analysis confirmed that EGCG time- and dose-dependently induced increases in miR-143 and miR-let-7a levels in 3T3-L1 preadipocytes. EGCG had no effect on miR-155 expression, but it significantly induced decreases in levels of Pref1/DLK1 (a target of miR-143) and HMGA2 (a target of miR-let-7a) mRNAs and proteins. These data suggest the selective effect of EGCG on particular types of miR family members. In addition, over-expression of either miR-143 or miR-let-7a inhibited 3T3-L1 preadipocyte growth in the absence of EGCG, as indicated by decreased cell number and by reduced cell viability. Whereas, treatment with the inhibitor of miR-143 antagonized the inhibitory effect of EGCG on cell number and cell viability. These data suggest a miR-143-dependent effect of EGCG on preadipocyte growth. Interestingly, EGCG mimicked the glutathione activator, such as N-acetyl-cysteine, to stimulate miR-143 and miR-let-7a, and pretreatment with the glutathione inhibitor, such as buthionine sulphoximine, blocked such EGCG effects. Moreover, an AMPK inhibitor, such as compound C, was found to reverse the effects of EGCG on miR-143 and miR-let-7 gene expressions. In conclusions, EGCG inhibits the growth of preadipocytes through activations of miR-143 and miR-let-7a molecules in glutathione- and AMPK-dependent ways. | en_US |