High fat diet induces differential age- and gender-dependent changes in neuronal function in Drosophila linked to redox stress

The prevalence of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, is steadily increasing, thus posing significant challenges to global healthcare systems. Emerging evidence suggests that dietary habits, particularly consumption of high-fat diets, may play a pivotal role in the development and progression of neurodegenerative disorders. Moreover, several studies have shed light on the intricate communication between the gut and the brain, linking gut health with neuroinflammation and its involvement in neurodegenerative processes. This study aims to assess the effects of a high-fat dietary intake on various aspects of neuronal function during aging in a gender specific manner to help understand the potential contributions of diet to neuronal function. To investigate the effects of a high-fat diet, Drosophila melanogaster was used and exposed to a standard normal food diet (NF) and a high-fat diet (HF). Adults were grouped at 10 and 45 days of age in male and female flies reared under the same conditions starting the HF diet at 5 days of age with data showing differential gender- and HF diet-induced phenotypes. Malondialdehyde (MDA) levels were higher in males at 10 and 45 days (p < 0.05), caspase-3 expression increased at 45 days (p < 0.01) implicating apoptosis induction and a reduced climbing activity at 10 and 45 days was apparent in females only (p < 0.01). Adult lifespan under both dietary conditions was unchanged when reared at 18°C but odour-associated learning ability was reduced in larvae reared in a HF diet throughout their development (p < 0.05). This is the first study to characterise effects of a HF diet on neuronal phenotypes in an age- and gender-specific manner in a Drosophila model. Our findings suggest a HF diet induces differential effects of neuronal dysfunction with age and sex-specific outcomes, characterised by enhanced oxidative stress and cell death impacting on behaviour.