ArticleFoods (Basel, Switzerland)2026
Multi-Omics Analyses Unveil the Effects of a Long-Term High-Salt, High-Fat, and High-Fructose Diet on Rats.
Article in Foods (Basel, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Supernatant of Water Extraction-Ethanol Precipitation ofFoods (Basel, Switzerland) · 2026Article
- Fast food, fast aging? A cross-sectional study in the UK.BMC public health · 2026Article
- Comparative Metabolomics Reveals the Nutritional Merit and Metabolic Basis of a Naturally Occurring White Variant inFoods (Basel, Switzerland) · 2026Article
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5 authors.
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Abstract
backgroundUnhealthy diets characterized by high salt, fat, and fructose content are established risk factors for metabolic and cardiovascular disorders and may have indirect effects on cognitive function. However, the combined impact of a high-salt, high-fat, and high-fructose diet (HSHFHFD) on systemic physiology and brain health remains to be fully elucidated.
methodsSprague-Dawley (SD) rats received a customized high-salt, high-fat diet supplemented with 30% fructose water for 18 weeks. Physiological and brain parameters were assessed, in combination with multi-omics analyses including brain proteomics and metabolomics, serum metabolomics, and gut microbiota profiling.
resultsHSHFHFD significantly elevated blood glucose, blood pressure, and serum levels of TG, TC, and LDL in rats. Serum metabolomic profiling identified over 100 differentially abundant metabolites in the Model group. Proteomics, metabolomics, and gut microbiome integration revealed pronounced alterations in both brain proteomic and metabolomic profiles, with 155 differentially expressed proteins associated with glial cell proliferation and 65 differential metabolites linked to fatty acid and amino acid metabolism, among others. Experimental validation confirmed marked upregulation of GFAP and Bax protein, concomitant with downregulation of ZO-1 and occludin. Furthermore, HSHFHFD perturbed the CREB signaling pathway, leading to diminished BDNF expression. The levels of inflammatory factors, including IL-6, IL-10, IL-1β and TNFα, were significantly elevated in the brain. Oxidative stress was evident, as indicated by elevated malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) activity, and altered NAD
conclusionsHSHFHFD-induced depletion of gut
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