dc.description.abstract | Obesity is a common disease, and it was associated with risk of cancer, diabetes, hypertention, and cardiovascular disease. Development of obesity results from increases in the cell number and fat accumulation of adipocyts, and is regulated by endocrine and nutritional factors. Insulin regulates mitogenesis and adipogenesis of fat cells and stimulates lipogenesis and inhibits lipolysis. By contrast, green tea catechins (once called vitamin P), especially (-)-epigallocatechin gallate (EGCG), inhibits proliferation and differentiation of fat cells and induces the apoptosis of preadipocytes and adipocytes. EGCG has been proposed as a chemopreventative for obesity and diabetes. However, relatively little is known about the mechanism of the action of EGCG on insulin-stimulated fat cell function. This study was designed to investigate the pathways of EGCG’’s modulation of the insulin-stimulated mitogenesis of 3T3-L1 preadipocytes. EGCG decreased insulin-induced increases in levels of phospho-insulin receptor (pIR), phospho-insulin receptor substrates 1, 2, and 3 (pIRS1, 2, and 3), phospho-Raf1, phospho-MEK1/2, and phospho-Erk1/2 proteins and induced further insulin-decreased pIRS4 level. In addition, EGCG reduced the insulin-stimulated associations of IR with IRS1 and IRS2. EGCG also reduced the association of IRS proteins with downstream signaling proteins. Besides, pretreatment with 67-kDa laminin receptor could antagonize the effect of EGCG on insulin-induced pMEK1/2 and pIRS2. These data suggest that EGCG exerts its antimitogenic effects via inhibiting insulin signaling by the 67-kDa laminin receptor-dependent pathway. Moreover, EGCG was more effective than epicatechin, epicatechin gallate, and epigallocatechin in changing the insulin-stimulated mitogenic signals. Results of this study may relate to the mechanism by which EGCG modulates insulin-related preadipocytes. | en_US |