Obesity is closely associated with various metabolic disorders, in which excess lipid accumulation plays a significant role. Adipocyte is one of the major sites for lipid storage during excess energy intake. Besides, non-adipose tissue may also deposit limited amount of lipid, but excess lipid accumulation may lead to cell dysfunction or cell death. Therefore, inhibition of adipogenesis and modulation of adipocyte functions as well as regulate lipid metabolism in various organs have been thought as a new trend for treatment of obesity-related disorders. We have recently shown that i.p. administration of indole-3-carbinol (I3C), an indolic compound derived from cruciferous vegetable, possesses anti-obesity activities in animals. Under acidic conditions, I3C can convert to other bioactive indolic derivatives, including 3,3’-diindolylmethane (DIM) and indolo[3,2-b]carbazole (ICZ), which have been shown to bind to the Ah receptor, one of the important factors in lipid metabolism and adipogenesis. Because the information of cruciferous vegetable derivatives on obesity is limited, this study is aimed at understanding the effects of I3C, DIM and ICZ on lipid metabolism and adipogenesis using both animals and cultured cell models, and the roles of Ah receptor in these processes will also be studied. In the first year study, high- and low-Ah receptor responsive mice will be orally or i.p. administered with I3C, and obesity-related factors will be determined. In the second year, primary hepatocytes and primary adipocytes will be isolated from high- and low-Ah receptor responsive mice, and the effects of I3C, ICZ, and DIM on lipid metabolism- and adipogenesis-associated factors will be analyzed. In the third year, human HepG2 hepatoma cells and murine 3T3-L1 preadipocytes will be used to investigate the effects of dietary indoles on lipid metabolism and adipocyte life cycle. In the fourth year, Ah receptor antagonist α-naphthoflavone (αNF)and Ah receptor siRNA will be applied to confirm the roles of Ah receptor in these processes. Results obtained from these experiments may provide information for understanding the molecular mechanisms through which indolic compounds derived from cruciferous vegetable in the roles of obesity-associated metabolic dysfunctions.
|Effective start/end date||8/1/11 → 7/31/12|