dc.description.abstract | Obesity is a common disease in the world and increases the risk of many metabolic syndrome related diseases, such as diabetes, hypertension, and cardiovascular disease. It is characterized by increased sizes and numbers of adipocytes so-called differentiation and mitogenesis. As white adipocytes store too much energy, which favors development of obesity, and beige and brown adipocytes consume energy to produce heat, which favors anti-obesity, the overall objective of this thesis was designed to investigate the effects of natural and synthetic compounds derived from betel nuts, green tea, or danshen on adipogenic differentiation of fat cells. Using 3T3-L1 white fat cells, we discovered that betel nut arecoline, but not arecaidine or quvacine, inhibited the 12-day differentiation of preadipocytes into adipocytes after 100 μM of treatment, as indicated by reduced triglyceride accumulation. This suggests the alkaloid-specific effect of betel nut on white fat cell adipogenesis. Using X9, D12, and D16 beige fat cells, we discovered that green tea epigallocatechin-3-gallate (EGCG) at 50 μM tended to reduce the number of cells and triglyceride accumulation during the 8-day differentiation and that D12 cells were more sensitive to respond to EGCG than other two fat cell types. This suggests beige cell type-dependent effect of EGCG. Using HIB1B brown fat cells, we discovered that EGCG, epicatechin gallate, epigallocatechin, gallic acid, but not epicatechin, could reduce the number of cells and triglyceride accumulation during the 8-day period of differentiation and that EGCG was more effective than other tea catechins. This indicates the catechin-specific effect. In addition, native danshen diterpenoids, such as dihydrotanshinone I (DHT-I), cryptotanshinone, and tanshinone IIA, were found to dose-dependently inhibit cell number and triglyceride accumulation during HIB1B cell differentiation and DHT-I was more effective than other two compounds. This indicates diterpenoid type-dependent effect of danshen. When synthetic danshen compounds, such as compounds 4, 5, and 6, were examined, they could inhibit triglyceride accumulation after 10 and 50 μM of treatment and the former two compounds were more effective than the last one compound. Moreover, depending on the concentrations, compounds 4, 5, and 6 were found in HIB1B brown fat cells to differentially alter the expressions of adipogenic differentiation marker genes, adipocyte protein (aP)-2, adiponectin, PR domain containing (PRDM)-16, resistin, and uncoupling protein (Ucp)-1. Taken together, these data suggest that the effect of the herbal compounds on the differentiation of fat cells varies with doses of treatment, chemical structures of native and synthetic compounds, adipogenic genes, and types of fat cell lines used, as well as may provide possible uses of tea catechin, betel nut alkaloid, and danshen diterpenoid for prevention and cure of fat cell-related diseases. | en_US |