Peter Gutenberger

The research surrounding my thesis work was on the effects of fasting on DNA damage repair, specifically looking to role of Adipose Triglyceride Lipase (ATGL) in mediating the response to DNA damage. Prior research has indicated that in cancer patients, fasting prior to receiving chemotherapeutics (DNA damage causing agents) was beneficial at increasing the effectiveness of treatment against the cancer, but also decreased negative side effects of the treatment in participants. Prior studies looking at irradiation in vivo experiments found increased survival in animals fasted prior to exposure to this physical mutagen. However, these experiments did not look at the role of ATGL in this response and at DNA-damage markers combined. As ATGL is a rate limiting step in lipolysis, we hypothesized that the positive effects from fasting seen in prior research were due to the ATGL mediated DNA damage response after exposure to a mutagen. We tested this at first by creating four groups: a group that was a sham group, one that was fed prior to irradiation, one that was fasted 24 hours prior to irradiation, and a final group fasted and given an ATGL inhibitor (ATGListatin). All of this mice were then sacrificed 4 hours after irradiation. This was followed up with a similar study that had the same groups (ATGL inhibition achieved through adenovirus shRNA) but were observed 24-hours post irradiation. The results from these experiment were inconclusive; expression of DNA damage proteins did not vary between irradiated groups. qPCRs looking at inflammatory gene expression and cell cycle arrest also showed no clear trends. Overall, the role of ATGL and fasting in DNA damage requires further study.