Academic Journal
Dietary Fatty Acids Differentially Modulate Hippocampal Glutamate-Related Gene Expression in Mice: Sex-Specific in Vivo and in Vitro Effects.
| Τίτλος: | Dietary Fatty Acids Differentially Modulate Hippocampal Glutamate-Related Gene Expression in Mice: Sex-Specific in Vivo and in Vitro Effects. |
|---|---|
| Συγγραφείς: | Romero-Muñoz L; Department of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain., Merino B; Department of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain., Sánchez-Hita E; Department of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain., Sanz-Martos AB; Department of Psychobiology, School of Psychology, National University for Distance Education (UNED), Madrid, Spain., Casado ME; Departments of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.; Research Institute La Princesa, Instituto De Salud Carlos III, and IMDEA Food Institute, CEIUAM + CSI, Madrid, Spain., Domingo-Martínez M; Department of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain., Plaza A; Department of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain., Morales L; Department of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain., García A; Centro De Metabolómica y Bioanálisis (CEMBIO), School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain., Fernández-Hernández C; Centro De Metabolómica y Bioanálisis (CEMBIO), School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain., Fernández-Felipe J; The Innate Immune Response Group, IdiPaz, Tumour Inmunology Lab, La Paz University Hospital, Madrid, Spain.; Faculty of Health Science, Universidad UNIE, Madrid, Spain., Olmo ND; Department of Psychobiology, School of Psychology, National University for Distance Education (UNED), Madrid, Spain., Marcos A; Department of Psychobiology, School of Psychology, National University for Distance Education (UNED), Madrid, Spain., Chowen JA; Departments of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.; Research Institute La Princesa, Instituto De Salud Carlos III, and IMDEA Food Institute, CEIUAM + CSI, Madrid, Spain., Ruiz-Gayo M; Department of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain., Cano V; Department of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain. |
| Πηγή: | Molecular nutrition & food research [Mol Nutr Food Res] 2026 Aug; Vol. 70 (15), pp. e70580. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 101231818 Publication Model: Print Cited Medium: Internet ISSN: 1613-4133 (Electronic) Linking ISSN: 16134125 NLM ISO Abbreviation: Mol Nutr Food Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Weinheim, Germany : Wiley-VCH, c2004- |
| Ιατρικοί όροι (MeSH): | Hippocampus*/metabolism , Hippocampus*/drug effects , Hippocampus*/cytology , Glutamic Acid*/metabolism , Dietary Fats*/pharmacology , Fatty Acids*/pharmacology, Palmitic Acid/pharmacology ; Diet, High-Fat/adverse effects ; Lauric Acids/pharmacology ; Astrocytes/drug effects ; Astrocytes/metabolism ; Neurons/drug effects ; Neurons/metabolism ; Oleic Acid/pharmacology ; Glutamine/metabolism ; Animals ; Male ; Female ; Mice, Inbred C57BL ; Mice ; Cells, Cultured |
| Περίληψη: | High-fat diets (HFDs) disrupt hippocampal (HIP) glutamatergic transmission, reducing synaptic plasticity and contributing to cognitive decline. While excessive dietary fat is known to alter glutamate (Glu) homeostasis, the specific effects of saturated versus unsaturated fatty acids and the role of sex remain unclear. We examined two HFDs, one enriched in oleic acid (OA) (UOLF, unsaturated) and another in palmitic and lauric acids (LAs) (SOLF, saturated), in young adult male and female mice. In males, both diets increased HIP Glu and glutamine (Gln) levels; however, only UOLF upregulated genes linked to Glu/Gln uptake and synthesis, suggesting an adaptive metabolic response. These changes were absent in females, indicating marked sex-dependent effects. In cultured HIP neurons and astrocytes, OA caused milder alterations than palmitic acid (PA) and selectively activated pathways that may lower extracellular Glu and enhance recycling. Lauric acid (LA) failed to activate protective mechanisms, implying it is a major driver of HIP dysfunction in males consuming saturated fats. Both diets disrupted the HIP Glu-Gln cycle in males, but only unsaturated fats triggered compensatory mechanisms that mitigate Glu accumulation. These findings emphasize the critical role of dietary fat composition and biological sex in shaping HIP Glu metabolism and glutamatergic function. (© 2026 Wiley‐VCH GmbH.) |
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| Grant Information: | PID2020-117422RB-C21 Ministerio de Ciencia e Innovación; PID2020-117422RB-C22 Ministerio de Ciencia e Innovación; Fundación Universitaria San Pablo-CEU (FUSP, GIR G20/5-04, ADIPOBRAIN) |
| Contributed Indexing: | Keywords: astrocyte; glutamate metabolism; high‐fat diets; lauric acid; neuron; oleic acid; palmitic acid |
| Substance Nomenclature: | 3KX376GY7L (Glutamic Acid) 2V16EO95H1 (Palmitic Acid) 0 (Lauric Acids) 1160N9NU9U (lauric acid) 2UMI9U37CP (Oleic Acid) 0 (Dietary Fats) 0RH81L854J (Glutamine) 0 (Fatty Acids) |
| Entry Date(s): | Date Created: 20260810 Date Completed: 20260810 Latest Revision: 20260909 |
| Update Code: | 20260910 |
| PubMed Central ID: | PMC13454707 |
| DOI: | 10.1002/mnfr.70580 |
| PMID: | 42572423 |
| Βάση Δεδομένων: | MEDLINE |
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