Differential effects of high-sucrose and high-fat diets on metabolic syndrome, BBB integrity, and hippocampal Aβ accumulation.
CF, A.G., E, M.A., E, D.l.C.H., & NP, G.C. (2026). Differential effects of high-sucrose and high-fat diets on metabolic syndrome, BBB integrity, and hippocampal Aβ accumulation.. Cellular and molecular biology (Noisy-le-Grand, France). https://doi.org/10.14715/cmb/2025.72.3.1
CF AG, E MA, E DlCH, NP GC. Differential effects of high-sucrose and high-fat diets on metabolic syndrome, BBB integrity, and hippocampal Aβ accumulation.. Cellular and molecular biology (Noisy-le-Grand, France). 2026; doi: 10.14715/cmb/2025.72.3.1
CF AG, E MA, E DlCH, et al. Differential effects of high-sucrose and high-fat diets on metabolic syndrome, BBB integrity, and hippocampal Aβ accumulation.[J]. Cellular and molecular biology (Noisy-le-Grand, France). 2026. DOI: 10.14715/cmb/2025.72.3.1.
@article{cf2026,
author = {Aguilar-Gamas CF and Martínez-Abundis E and De la Cruz-Hernández E and Gómez-Crisóstomo NP},
title = {Differential effects of high-sucrose and high-fat diets on metabolic syndrome, BBB integrity, and hippocampal Aβ accumulation.},
journal = {Cellular and molecular biology (Noisy-le-Grand, France)},
year = {2026},
doi = {10.14715/cmb/2025.72.3.1},
note = {PMID: 42322577},
}
TY - JOUR AU - Aguilar-Gamas CF AU - Martínez-Abundis E AU - De la Cruz-Hernández E AU - Gómez-Crisóstomo NP TI - Differential effects of high-sucrose and high-fat diets on metabolic syndrome, BBB integrity, and hippocampal Aβ accumulation. T2 - Cellular and molecular biology (Noisy-le-Grand, France) PY - 2026 DO - 10.14715/cmb/2025.72.3.1 AN - PMID:42322577 ER -
Metabolic syndrome (MS) is a global health problem and a recognized risk factor for cognitive impairment and Alzheimer's disease (AD), but the different effects of specific dietary components on MS-related neurological damage remain unclear. This study investigated the effects of long-term high-calorie diets on metabolic parameters, blood-brain barrier (BBB) integrity, and hippocampal β-amyloid (Aβ) accumulation. Male Wistar rats were fed a control diet, a high-sucrose diet (HSD, 30% sucrose in drinking water), or a high-fat diet (HFD, 30% lard) for 12 months. The study assessed metabolic syndrome parameters, spatial memory (Morris water maze), BBB permeability (Evans blue staining), tight junction proteins (ZO-1, Occludin), and the levels of Aβ and its transporters (LRP1, RAGE). The results showed that both HSD and HFD induced central obesity, increased BBB permeability, and spatial memory deficits in rats; however, disruption of the blood-brain barrier was not associated with changes in tight junction protein expression. Notably, hippocampal Aβ accumulation increased only in the high-fat diet group (HFD group) after 8-12 months, associated with a significant downregulation of the Aβ clearance receptor LRP1, while no changes were observed in RAGE. In contrast, the high-fat diet group (HSD group) exhibited more extensive metabolic syndrome-related alterations, including hyperglycemia and hypertension. Our results suggest that while both sucrose- and fat-based high-calorie diets impair the integrity of the blood-brain barrier and cognitive function, only high-fat intake promotes hippocampal Aβ accumulation by downregulating LRP1. These results suggest that although both dietary patterns contribute to metabolic syndrome and cognitive impairment, high-fat intake may pose a more specific risk to Alzheimer's disease pathology.