DIETARY ω-6:ω-3 SUPPLEMENTATION AND HIGH-SUGAR DIET: METABOLIC AND FUNCTIONAL EFFECTS IN Drosophila melanogaster

Inflammation, promoted by factors such as the Western diet, contributes to chronic and neurodegenerative diseases. Consumption of ω6 and ω3 polyunsaturated fatty acids (PUFAs) may be anti-inflammatory and neuroprotective, but their ideal proportion in the diet is still unclear. Based on this, the present study investigated the preventive effects of different ω6:ω3 ratios combined with vitamin E (α-tocopherol) on inflammation and neurodegeneration induced by a high-sugar diet (HSD) in Drosophila melanogaster. Vitamin E was included due to its role preventing lipid peroxidation of PUFAs. Adult female and male wild-type fruit flies (Canton S) were exposed for 10 days to different experimental conditions: control diet (CD), HSD, HSD with vitamin E (HSDE) and HSDE plus ω6:ω3 10:1, 4:1 and 2:1 ω6:ω3 ratios. The 10:1 ratio represented the typical profile of a Western diet, and the 2:1 ratio was selected based on its potential anti-inflammatory effects. The inflammatory marker Upd3, metabolic parameters (circulating glucose and total triglycerides) and neurofunctional capacities (phototactic and climbing tests) and survival were evaluated. Confirming results already reported in the literature, the HSD increased the relative expression of Upd3 (~10 times vs. CD; p<0.0001), suggesting systemic inflammation; it also promoted an increase in total glucose and TG levels and a reduction in the neurofunctional capacity of Drosophila. Regarding the experimental diets, all groups supplemented with vitamin E exhibited lower Upd3 expression than the HSD, which may indicate a protective effect associated with α-tocopherol. A significant reduction in glycemia was favored by the HSDE 2:1  in females (~1500 mg/dL HSD to ~480 mg/dL; p<0.0001) and males (~1400 mg/dL HSD to ~520 mg/dL; p<0.0001). In functional assays, exposure to HSDE 2:1 promoted a three-fold improvement in climbing performance compared to HSD (p<0.01); the phototaxis assay revealed an approximately six-fold improvement in phototactic activity in the HSDE 2:1 group compared to the HSD group (p<0.01). Regarding the survival assay, HSDE 10:1 demonstrated effects similar to HSD, decreasing the life expectancy of Drosophila, whereas HSDE 2:1 improved survival by 17% and 8.7%  when compared to HSD in males and females, respectively. Overall, the findings indicate that a 2:1 ω6:ω3 supplementation protects Drosophila melanogaster against the harmful effects of a high-sucrose diet. This supports balanced PUFA intake as a preventive nutritional strategy and gives a basis for future translational research in humans.