The Study of the Relationships among Anti-Obesity Activity, Adipogenesis, and Adipose Angiogenesis of Vegetable Indolic Derivatives---Involvement of the Ah Receptor/Arnt ?(III)

Obesity is closely associated with various metabolic disorders, and excess lipid accumulation and adipose angiogenesis play significant roles in these pathological processes. In addition to decrease energy intake and increase energy consumption, inhibition of adipogenesis, modulation of adipocyte functions, as well as suppression of adipocyte angiogenesis have been proposed as a new trend for alternative treatment of obesity and its related diseases. Ah receptor (AhR)/AhR translocator protein (Arnt) pathway has been indicated to be involved in both adipogenesis and angiogenesis pathways. We have previously indicated that indole-3-carbinol (I3C), an indolic compound derived from cruciferous vegetable, possesses anti-obesity activities in animals, and inhibits angiogenic activities in endothelial cells. 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 AhR. Because the information for these indole derivatives on obesity is limited, this study is aimed at investigating the effects of I3C, DIM and ICZ on adipogenesis and adipose angiogenesis by using human adipose tissues and cultured cells, and the roles of AhR/Arnt in these processes will also be clarified. In the first year study, we will analyze the expression of adipogenesis- and angiogenesis-assocated factors in different sources of adipose tissues obtained from human subjects with different BMIs. Polymorphism of various genes will also be explored. Besides, the effects of these indoles on primary adipocytes from different sources will be studies. In the second year, murine 3T3-L1 preadipocytes will be used to investigate the effects of dietary indoles on adipogenesis and adipose angiogenesis-associated factors. siRNAs for AhR and Arnt will be introduced to identify the roles of AhR and Arnt in these processes. In the third year, the association among dietary indoles, adipogenesis, angiogenesis, and AhR/Arnt pathway will be studies by using different sources of cultured cells. Results obtained from these experiments may provide information for understanding the molecular mechanisms through which dietary indoles and the AhR/Arnt in the roles of obesity.