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

The prevalence of neurodegenerative diseases, such as Alzheimers disease and Parkinsons disease, is steadily increasing, posing significant challenges to global healthcare systems. Emerging evidence suggests that dietary habits, particularly consumption of high-fat diets specify which fats, 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, known as the gut-brain axis 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 and following gender separation 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 standard normal food diet (NF) and high-fat diet (HF). Adults were grouped at 10 and 45 days of age in male and female flies reared under the same conditions. Multiple assays were conducted, showing differential gender- and HF diet-induced oxidative stress levels as determined by malondialdehyde (MDA) measurements, enhanced caspase-3 expression and reduced climbing activity. Adult lifespan under both dietary conditions was unchanged but odour-associated learning ability was reduced in larvae reared in a HF diet. This is the first study to characterise effects of diet on neuronal phenotypes in an age- and gender-specific manner in a Drosophila model. Our findings suggest a HF diet induces differential forms of neuronal dysfunction with age and sex-specific outcomes, characterised by enhanced oxidative stress and cell death which impacts on neuronal and behavioural functions.