(P27-016-23) The Impact of Dietary Folic Acid Supplementation and Hypoxia on Health Outcome Using a Fly Model System

Objectives: One-carbon (1C) metabolism is a metabolic network that integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. It plays an essential role in the regulation of cell proliferation, stress resistance, and embryonic development. The natural form of the B vitamin, folate, is central in 1C, as well as the synthetic form of the vitamin referred to as folic acid. In the cell, 1C plays an essential role in nucleotide synthesis of purines, removal of uracil from DNA, and methylation, through the metabolism of homocysteine and generation of S-adenosylmethionine. Our work has previously shown that dietary folic acid supplementation is beneficial after hypoxia, however, the mechanisms through which this occurs remain unknown. Little is known about the molecular mechanisms underlying the cellular responses to lack of oxygenation and how to prevent damage once a reduction in O2 supply has occurred. The aim of our study is to investigate the how folic acid supplementation impacts hypoxia outcome.

Methods: We used W1118 male and female Drosophila melanogaster, they were put on folic acid supplemented diet of 100uM as well as control diet with the minimal amount of folic acid. Offspring from these crosses were exposed to 2 hours of 1% oxygen for a period of 2 hours after which flies were returned to normoxic conditions to model reperfusion. Mortality rate was recorded for one week after hypoxia treatment.

Results: We observed that 50uM of folic acid reduced the number of dead flies whereas 100uM increased the number of dead flies. Furthermore, we observed changes in climbing behavior of flies 3 hours after hypoxia.

Conclusions: We are currently investigating apoptosis and oxidative stress mechanisms in brain tissue of flies to determine potential mechanisms.

Funding Sources: American Heart Association (Nafisa M. Jadavji; 20AIREA35050015)