Metabolic Disturbance of High-Saturated Fatty Acid Diet in Cognitive Preservation

Abstract

first_pagesettingsOrder Article Reprints Open AccessArticle Metabolic Disturbance of High-Saturated Fatty Acid Diet in Cognitive Preservation by Antonio Rivas-Domínguez 1ORCID,Himan Mohamed-Mohamed 2,Margarita Jimenez-Palomares 3ORCID,Victoria García-Morales 3ORCID,Laura Martinez-Lopez 1,Manuel Luis Orta 1,Juan José Ramos-Rodriguez 2,*,†ORCID andBeatriz Bermudez-Pulgarin 1,† 1 Department of Cellular Biology, University of Seville, 41009 Seville, Spain 2 Department of Physiology, Faculty of Health Sciences (Ceuta), University of Granada, 51001 Ceuta, Spain 3 Department of Biomedicine, Biotechnology and Public Health, University of Cádiz, 11003 Cádiz, Spain * Author to whom correspondence should be addressed. † These authors contributed equally to this work. Int. J. Mol. Sci. 2023, 24(9), 8042; https://doi.org/10.3390/ijms24098042 Received: 31 March 2023 / Revised: 16 April 2023 / Accepted: 26 April 2023 / Published: 28 April 2023 (This article belongs to the Special Issue Research on Neural and Cognitive Molecular Mechanisms of Memory and Executive Control) Download Browse Figures Review Reports Versions Notes Abstract Aging continues to be the main cause of the development of Alzheimer’s, although it has been described that certain chronic inflammatory pathologies can negatively influence the progress of dementia, including obesity and hyperlipidemia. In this sense, previous studies have shown a relationship between low-density lipoprotein receptor (LDLR) and the amyloid-beta (Aβ) binding activity, one of the main neuropathological features of Alzheimer’s disease (AD). LDLR is involved in several processes, including lipid transport, regulation of inflammatory response and lipid metabolism. From this perspective, LDLR−/− mice are a widely accepted animal model for the study of pathologies associated with alterations in lipid metabolism, such as familial hypercholesterolemia, cardiovascular diseases, metabolic syndrome, or early cognitive decline. In this context, we induced hyperlipidemia in LDLR−/− mice after feeding with a high-saturated fatty acid diet (HFD) for 44 weeks. LDLR−/−-HFD mice exhibited obesity, hypertriglyceridemia, higher glucose levels, and early hepatic steatosis. In addition, HFD increased plasmatic APOE and ubiquitin 60S levels. These proteins are related to neuronal integrity and health maintenance. In agreement, we detected mild cognitive dysfunctions in mice fed with HFD, whereas LDLR−/−-HFD mice showed a more severe and evident affectation. Our data suggest central nervous system dysfunction is associated with a well-established metabolic syndrome. As a late consequence, metabolic syndrome boots many behavioral and pathological alterations recognized in dementia, supporting that the control of metabolic parameters could improve cognitive preservation and prognosis.