dc.description.abstract | Green tea catechins, particularly epigallocatechin gallate (EGCG), have been reported to reduce body weight and regulate fat cell activity. Although EGCG was found to mediate the growth and differentiation of white, beige, and brown fat cells, the exact mechanisms of the actions of EGCG and other structurally-related tea catechins, such as epicatechin (EC), epigallocatechin (EGC), and epicatechin gallate (ECG), on beige adipogenic differentiation are still not clear. Thus, the objective of the present thesis was designed to investigate the effect of tea catechin on the differentiation of D12 beige fat cells. The results indicated catechin-specific effect of tea on beige cell differentiation, as indicated by changes in the total triglyceride accumulation. Generally, EGCG was more effective than catechin, EC, ECG, and EGC to reduce the accumulation of triglyceride, as well as reducing the number of cells. In addition, EGCG dose-dependently suppressed the expression of adipogenic differentiation marker genes in D12 beige cells, including C/EBPα, Cidea, PGC-1α, PPARγ, TBX1, and UCP-1. Since the differentiation of white fat cells can be regulated by microRNA (miR)-let-7a and miR-143, changes in their expression during adipogenic differentiation of D12 cells induced by EGCG were accessed. The results showed that miR-let-7a and miR-143 significantly increased their expression levels during the 8-day period of beige fat cell differentiation and that EGCG significantly inhibited miR-let-7a mRNA expression and increased miR-143 mRNA levels in a dose-dependent way. Also, EGCG induced significant increases in the HMGA2 (a target of miR-let-7a) mRNA and protein levels and had no significant effect on DLK1 (a target of miR-143) mRNA expression. Using 3T3-L1 white and HIB1B brown fat cells for comparison with the effect of EGCG on the differentiation among three fat cell types, we found that EGCG induced increases in levels of Cidea, PGC-1α and UCP1 mRNAs and decreases in levels of C/EBPα and PPARγ mRNAs during the differentiation of white fat cells. Interestingly, EGCG inhibited the mRNA expression of all C/EBPα, Cidea, PGC-1α, PPARγ, and UCP1 mRNAs during brown fat cell differentiation. In conclusions, the effect of EGCG on the process of adipogenic differentiation appears fat cell type-independent and catechin-dependent. As obesity is associated with fat cell activity and as the activities of beige and brown fat cells are associated with cachexia of cancer patients, the results of the present thesis may provide the evidence by which tea catechin exert its effects on obesity and cancer cachexia. | en_US |