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

Obesity is closely associated with various metabolic disorders, in which excess lipid accumulation and adipose angiogenesis play significant roles. Thus, inhibition of adipogenesis, modulation of adipocyte functions, as well as suppression of adipocyte angiogenesis have been thought as a new trend for treatment of obesity. We have previously indicated that indole-3-carbinol (I3C), an indolic compound derived from cruciferous vegetable, possesses anti-obesity activities in animals when administered intraperitoneally. In cultured cells, I3C shows inhibitory effects on 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 Ah receptor (AhR), one of the important factors in the processes of adipogenesis and angiogenesis. Because the information of cruciferous vegetable indole derivatives on obesity is limited, this study is aimed at understanding the effects of I3C, DIM and ICZ on adipogenesis and adipose angiogenesis by using both animals and cultured cell models, and the roles of AhR and Arnt in these processes will also be clarified. In the first year study, high- and low-AhR responsive mice will be orally administered with I3C, and the obesityand adipose angiogenesis-related factors will be determined. In the second year, primary adipocytes isolated from high- and low-AhR responsive mice will be used to study the effects of I3C, ICZ, and DIM on and adipogenesis- and adipose angiogenesis-associated factors. In the third year, murine 3T3-L1 preadipocytes will be used to investigate the effects of dietary indoles on adipogenesis and adipose angiogenesis-associated factors. Besides, the AhR antagonist, α-naphthoflavone (αNF), and Arnt siRNA will be introduced to confirm the roles of AhR and Arnt 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.