Effects of dietary aspartate supplementation on mitochondrial metabolism in Drosophila melanogaster

Obesity-associated health complications are on the rise, increasing the burden on healthcare systems in developed countries. These complications include both insulin resistance and deregulated mitochondrial metabolism. To combat obesity some individuals incorporate artificial sweeteners into their diet. Aspartame, one of the most widely used sweeteners, is found in diet sodas and sugar free candies. Interestingly, aspartame consumption is associated with impaired mitochondrial function and lipid droplet accumulation. Further, the molecular mechanisms relating aspartame consumption to insulin resistance and obesity are incompletely understood. Our study aims to investigate the role of aspartame in regulating mitochondrial fission and insulin action. We supplemented standard Drosophila diets with aspartame in different doses (0.05%, 0.1%, and 0.5%). We report that wild type (Oregon R) flies consuming a standard diet supplemented with aspartame develop more rapidly and gain more weight than un-supplemented controls. Expression levels of fis1, a gene that promotes mitochondrial fission, are statistically significantly decreased in the low dose group (0.05%), relative to controls. To test for interactions between aspartame consumption and insulin action, we will utilize a temperature-sensitive (InRY902C) mutant strain, in which insulin receptor activity is impaired when reared at 29°C. We hypothesize that InRY902C flies will exhibit increased body weight and reduced fis1 expression when consuming aspartame, due to additive metabolic impairments. These results would suggest that aspartame consumption worsens mitochondrial health in insulin-resistant individuals. Overall, this study provides insight into how artificial sweeteners, while consumed to prevent obesity, can promote obesity-associated complications. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.