With modern lifestyles increasingly dominated by processed and fatty foods, high-fat diets (HFDs) have been linked to conditions like obesity, diabetes and metabolic disorders. More recently, researchers have also begun investigating the impact of such diets on brain health.
The research team used Drosophila melanogaster, the common fruit fly, as their model. Fruit flies share many metabolic and neural pathways with humans, making them ideal for studying complex biological processes like memory formation. The researchers fed the flies either a normal diet or and high-fat diets for seven days, then assessed changes in their metabolism and memory.
Flies on the high-fat diet showed increased levels of triacylglycerol (TAG), glucose, and intestinal lipid accumulation—indicating altered lipid and glucose metabolism. Most strikingly, the high-fat diets -fed flies demonstrated significant impairments in intermediate-term memory (ITM) and long-term memory (LTM), though short-term memory remained intact. This cognitive decline was linked to disruptions in autophagy and lysosomal function.
“Our findings suggest that diet-induced cognitive decline is not irreversible and may be improved by lifestyle interventions that promote autophagy, such as exercise or intermittent fasting,” said Associate Professor Ayako Tonoki from the Graduate School of Medical and Pharmaceutical Sciences.
Understanding how diet impacts autophagy and memory could pave the way for early preventive strategies against neurodegenerative diseases, underscoring the importance of healthy eating for lifelong brain health.
Reference: Yue T, Jiang M, Onuki K, Itoh M, Tonoki A (2025) High-fat diet impairs intermediate-term memory by autophagic-lysosomal dysfunction in Drosophila. PLoS Genet 21(8): e1011818. https://doi.org/10.1371/journal.pgen.1011818
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