ArticleFrontiers in aging neuroscience2026
High-saturated-fat diet drives female-biased neurodegeneration in
Article in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: Dietary saturated fat intake has been increasingly linked to dementia risk, yet the mechanisms through which high-fat diets (HFDs) compromise neuronal integrity remain poorly defined. The model organism Methods: Flies were fed diets containing 30% (w/v) fat from 2 oils with varying saturated-fat content and were assessed for lifespan and climbing ability. Immunohistochemistry and confocal imaging were used to evaluate brain tissue integrity, quantify vacuoles, and assess oxidative stress and activation of an inflammatory pathway. Genetically encoded and UAS-driven fluorescent reporters, along with confocal imaging, were used to assess autophagy and autophagic flux. Results: Both HFDs shortened lifespan but only the highest saturated-fat source (coconut oil) uniquely produced a female-specific decline in climbing ability and significant neurodegeneration, compared to lard and control diets. Mechanistic evaluation revealed no activation of the NF-κB homolog Conclusion: These findings identify oxidative stress and disrupted autophagy as key mediators of saturated-fat-induced neuronal decline and highlight a sex-specific vulnerability to dietary fat composition. This work establishes
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