Comparative Study of Intermittent Fasting and High Fat Diet in Preventing Amnesia in an In Vivo Model

Abstract

The increase prevalence of Alzheimer's disease has intensified the search for non pharmacological interventions, with dietary regimens like intermittent fasting (IF) and high-fat diets (HFD) showing promise yet possessing paradoxical metabolic effects. A direct comparison of their efficacy in a controlled model is lacking. This study aimed to directly compare the prophylactic potential of IF and HFD against metabolic and inflammatory markers associated with cognitive decline in a zebrafish larvae model. Zebrafish larvae were allocated to four groups for 12 weeks based on their diet variation. Survival, biometric data (weight), lipid profiles (cholesterol, triglycerides), and gene expression of metabolic (srebf1c and pparab) and pro inflammatory (tnf-α and il1b) markers were analyzed. The HFD group exhibited significantly reduced survival, increased weight, dyslipidemia, and upregulated expression of both metabolic and pro-inflammatory genes. In contrast, HFD+IF2 regimen completely mitigated the HFD-induced lethality, normalized lipid levels and weight, and potently suppressed the pro-inflammatory cytokine expression to baseline levels. The HFD+IF1 group showed intermediate benefits, indicating that late intervention was less effective than a proactive strategy. Intermittent fasting, when implemented concurrently with a high-fat diet, is a powerful intervention that fully counteracts the detrimental metabolic and inflammatory effects of the diet. The potent anti-inflammatory effect of IF provides a compelling mechanistic rationale for its potential in preventing diet-associated amnesia, highlighting the critical importance of dietary timing in maintaining brain health.