Cognitive impairment in metabolically-obese, normal-weight rats: identification of early biomarkers in peripheral blood mononuclear cells

Autor: Paula Oliver, Margalida Cifre, Andreu Palou
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
SORL1
Hippocampus
lcsh:Geriatrics
ratas
lcsh:RC346-429
0302 clinical medicine
Leukocytes
Cognitive decline
dieta
Cognition
Research Article
sinapsinas
Blood cells
medicine.medical_specialty
MONW
leucocitos
hipocampo
Diet
High-Fat
Peripheral blood mononuclear cell
03 medical and health sciences
Cellular and Molecular Neuroscience
Insulin resistance
Internal medicine
medicine
Animals
Dementia
Cognitive Dysfunction
Obesity
Rats
Wistar
Maze Learning
obesidad
Molecular Biology
lcsh:Neurology. Diseases of the nervous system
business.industry
Synapsins
medicine.disease
MCI
Diet
Rats
Adaptor Proteins
Vesicular Transport
lcsh:RC952-954.6
030104 developmental biology
Endocrinology
aprendizaje por laberinto
Leukocytes
Mononuclear
animales
Neurology (clinical)
business
Biomarkers
030217 neurology & neurosurgery
Zdroj: Molecular Neurodegeneration, Vol 13, Iss 1, Pp 1-14 (2018)
Molecular Neurodegeneration
ISSN: 1750-1326
DOI: 10.1186/s13024-018-0246-8
Popis: Background: Metabolically-obese, normal-weight (MONW) individuals are not obese in terms of weight and height but have a number of obesity-related features (e.g. greater visceral adiposity, insulin resistance, and increased risk of cardiovascular disease). The MONW phenotype is related to the intake of unbalanced diets, such as those rich in fat. Increasing evidence shows a relationship between high-fat diet consumption and mild cognitive impairment and dementia. Thus, MONW individuals could be at a greater risk of cognitive dysfunction. We aimed to evaluate whether MONW-like animals present gene expression alterations in the hippocampus associated with an increased risk of cognitive impairment, and to identify early biomarkers of cognitive dysfunction in peripheral blood mononuclear cells (PBMC). Methods: Wistar rats were chronically fed with a 60% (HF60) or a 45% (HF45) high-fat diet administered isocalorically to control animals to mimic MONW features. Expression analysis of cognitive decline-related genes was performed using RT-qPCR, and working memory was assessed using a T-maze. Results: High-fat diet consumption altered the pattern of gene expression in the hippocampus, clearly pointing to cognitive decline, which was accompanied by a worse performance in the T-maze in HF60 animals. Remarkably, Syn1 and Sorl1 mRNA showed the same expression pattern in both the hippocampus and the PBMC obtained at different time-points in the HF60 group, even before other pathological signs were observed. Conclusions: Our results demonstrate that long-term intake of high-fat diets, even in the absence of obesity, leads to cognitive disruption that is reflected in PBMC transcriptome. Therefore, PBMC are revealed as a plausible, minimally-invasive source of early biomarkers of cognitive impairment associated with increased fat intake.
This work was supported by the Spanish Government: EPIMILK - AGL2012-33692- and INTERBIOBES - AGL2015-67019-P (AEI, MINECO/FEDER, EU) and by the University of the Balearic Islands: IBIFLEX - FA38/2016-. The Laboratory of Molecular Biology, Nutrition and Biotechnology is a member of the European Research Network of Excellence NuGO (The European Nutrigenomics Organization, EU Contract: FOOD-CT-2004-506360 NUGO). MC is the recipient of a fellowship from the Spanish Government.
Databáze: OpenAIRE
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