Abstract 592: Nutrigenomic Screening of Functional Foods Regulating Gluconeogenesis: A Zebrafish Pilot Study

Introduction/rationale: Current anti-diabetic drug treatments have a variety of adverse side effects. Identifying functional foods with anti-diabetic properties may be the key to preventing and managing T2DM while minimizing side effects. Studies found that Pck-1 gene is often down-regulated by anti-diabetic drugs, as its enzyme is responsible for catalyzing the rate-limiting step of gluconeogenesis. In our study, we screened for functional foods that can down-regulate the expression of the Pck-1 gene. The newly emerged zebrafish (Danio rerio) is aptly suited for in vivo nutrigenomic screening due to its large clutch size and conservation of molecular pathways with humans, including those involved in glucose regulation. Methods: We exposed zebrafish larve (Tg(Pck-1:luc), a luminescent reporter line for Pck-1), at 4 days post fertilization (dpf) to extracts from forty functional fruits and vegetables. The level of Pck-1 expression was quantified by luminescence at 6 dpf. Extracts which resulted in a lower reading of luminescence were interpreted as functional foods that could successfully down-regulate Pck-1 expression, and therefore may be potential therapeutic for T2DM. We further validated our results using a fluorescent reporter line for Pck-1 (Pck-1:eGFP). Results: We completed toxicity assays on the functional food extracts to determine the optimal concentrations and conditions for nutrigenomic screening. Preliminary results show that bamboo and cherry extracts significantly reduced Pck-1 gene expression by two fold (p<0.05). Other functional food extracts, such as grape, cucumber, cabbage, spinach, flat beans, and lemon also reduced Pck-1 gene expression. Interestingly, garlic extracts increased Pck-1 gene expression. Conclusion and Discussion: We identified two functional food extracts that successfully reduced Pck-1 expression in zebrafish models. Increasing the intake of these two functional foods may regulate blood glucose levels in T2DM patients. Further research elucidating the active ingredient in these foods is required. The Pck-1 zebrafish model can be employed for further nutrigenomic screening and/or for drug discovery purposes.