high-Fat โDietโ Linked to Memory Impairment in Fruit Flies,Reversible Through Autophagyโค Enhancement
New research published in PLoS Genetics demonstrates a link between a high-fat diet (HFD) and impaired intermediate- and long-term memory in fruit fliesโ (Drosophila โคmelanogaster),with theโค underlyingโ mechanism appearing to be โฃa disruption in the cellular process of autophagy. Importantly, the study suggests this memory impairment is not permanent โขand can be improved โbyโ interventions that boost autophagy.
Researchers โขled โคby Dr. Tonoki observed that flies fed an โHFD for โฃsevenโ days exhibited significantly elevated levels of lipid-triacylglycerolโ (TAG) and โคcirculating glucose, alongside โincreased lipid accumulation in the intestines. This indicates the HFD alteredโ the flies’โ metabolic processesโ related to glucose and lipid โคmanagement.
To assess theโข impact on cognitive function, the team tested the flies’ memory formation using odor-conditioning paired with mild electric shock.While short-term memoryโข (STM) remained โขunaffected, intermediate-term memory (ITM) โandโ long-term memory (LTM) were โsignificantly โขimpaired in flies consuming the HFD.
Further investigation revealedโฃ a correlationโข between the HFD and autophagic dysfunction. Levels of Ref(2)p, a protein normallyโฃ broken down by autophagy, were elevated in HFD-fedโค flies. Together, theโข ratio of Atg8a-II/I – a marker indicating autophagosome formation – was reduced, suggesting a declineโข in autophagicโ activity.
To confirm autophagy’s role, researchers selectivelyโ suppressed the autophagy protein Atg1โค inโค adult neurons,โ which resulted in ITM โimpairment mirroring the effects of the HFD. Conversely, enhancing autophagy through overexpression of Atg1, suppression of the autophagy inhibitor Rubicon, or treatment โขwith the autophagy inducer rapamycin, reversed the memory deficits observed in the HFD-fed flies.
The study โฃpinpointed a specific point of failure within the autophagyโฃ process: the fusion of autophagosomes and lysosomes into autolysosomes, where cellular waste is degraded. HFD-fed โขfliesโ showed an abundance of both autophagosomes and lysosomes, but no corresponding increase in autolysosome numbers, indicating a blockage in the final stage of autophagy.gene expression analysis โฃrevealed โคdownregulation of genes related to lysosome signaling.โ โFurther supporting this, inhibiting lysosomal function โalso reduced ITM.
“This research advances โคour understanding of how dietary habits influence brain health,” explains Dr. Tonoki.โฃ “Our findings โmay also accelerate the identification of autophagy-enhancing โคinterventions – including specific nutrients and therapeutic agentsโ – to combat diet-induced cognitive decline and preserve cognitionโ in the aging population.” The researchers emphasize that the cognitive risks associated withโข HFD are potentially reversible โand highlight the possibilityโ of โpreventative strategies against metabolic and โneurodegenerativeโข disorders through lifestyle interventions promoting autophagy, such as exercise or intermittent fasting.
Source: Yue, T.,โข et al. (2025). High-fat dietโฃ impairs intermediate-term memory by autophagic-lysosomal dysfunction in Drosophila. PLoS Genetics. doi.org/10.1371/journal.pgen.1011818.
