View Program - 63rd Annual Drosophila Research Conference

Obesity predisposes a person to an array of life-threatening metabolic disorders including diabetes, high blood pressure, heart attack, and cancer. The long-term treatment for such diseases is often less effective in providing a complete cure, and the cost for it creates excessive economic burden. Thus, new and more effective therapeutic approaches are under review. In the last two decades, Neprilysins (Neps), the membrane bound metallo-ectopeptidases, have become targets to treat obesity and related disorders for their correlation with high fat and high sugar diet induced obesity and diabetes. Thus, the mechanisms by which Neps regulates obesity need to be explored. In our recent published work, we show that knock-out of the Drosophila specific gene Neprilysin like 15 (Nepl15^ko), which has overall higher expression in the wild type adult male compared to female flies, results in significant reduction of stored glycogen and lipids only in adult males, but increases glycogen in females. Although, the mutant flies show similar food intake compared to the controls. To further dissect the effects on the expression of the key enzymes in glycogen and lipid homeostasis pathway, we recently find that Nepl15^koadult males but not females have significant reduction in the expression of Glycogen Synthase and Glycogen Phosphorylase transcripts compared to controls. In addition, we have performed longevity and climbing assay to investigate the effect of Nepl15 loss of function on overall health and physiological motor activity. We reveal that the Nepl15^koadult males have similar life span, but Nepl15^kofemales show significantly extended life span compared to the controls. Both Nepl15^ko adult males and females flies show enhanced ability of climbing in an age dependent manner compared to the controls. For example, whereas there is no difference in climbing ability between the mutant and control males and females up to 30 days of age, the mutant flies of both sexes exhibit significantly higher ability for climbing at the age of 40 days. Thus, our research reveals that mutation in the Nepl15 provides health benefits in females, and keeps the physical activeness for longer in both sexes due to changes in nutrient homeostasis. In the future, we will investigate the lipid homeostasis pathway and energy metabolism in these flies. This project is funded by Arkansas NIH-INBRE grant.

The loss of function mutation in the Drosophila Neprilysin Like 15 changes expression of key enzymes involved in glycogen homeostasis, and effects longevity in sex specific manner, but exerts similar effects on motor activity in both sexes