| dc.description.abstract | Obesity, a common disease resulting from mitogenesis and lipid accumulation (so-called adipogenesis) of fat cells, is associated with the risks of cancers, diabetes, hypertension, and cardiovascular disease. Development of obesity can be regulated by endocrine and nutritional cues based on a variety of laboratory studies. Insulin (INS) was reported to stimulate mitotic clonal expansion and adipogenesis during fat cell differentiation in additional to stimulating lipogenesis and inhibiting lipolysis. In contrast, green tea polyphenols (the so-called vitamin P), especially the catechin, (-)-epigallocatechin gallate (EGCG), was found to inhibit proliferation and differentiation of fat cells, to induce the apoptosis of preadipocytes and adipocytes, to stimulate fat oxidation, and to be proposed as an obesity chemopreventative. But, determining whether EGCG acts to regulate the stimulatory effect of INS on the mitogenesis of fat cells is still not clear. In this thesis using 3T3-L1 preadipocytes as the research cell model, I found that INS at 1-1000 nM could stimulate the growth of 3T3-L1 preadipocytes as indicated by increased cell number and BrdU incorporation. The EC50-100 of INS was about 100 nM after 2~4 days of treatment. Also, INS stimulated activities of INS receptor (INSR), insulin receptor substrate 1 (IRS-1), and MEK1, respectively, as indicated by increased phosphorylation of INSR, IRS-1, and Erk proteins. However, pretreatment of preadipocytes with EGCG (10-50 μM) resulted in significant decreases in the INS-induced increases in their cell number, BrdU incorporation, activities of INSR, IRS-1, and MEK-1, and the association of INSR with IRS-1. These data suggest that EGCG can inhibit preadipocyte mitogenesis by reduction of INS-mediated signaling in these cells. | en_US |