Title:	Early-life metabolic dysfunction impairs cognition and mitochondrial function in mice
Authors:	Vilela, Wembley Rodrigues Bellozi, Paula Maria Quaglio Picolo, Victor Luna Cavadas, Bruna Neves Marques, Keila Valentina Silva Pereira, Louise Tavares Garcia Guirao, Ainhoa Rodriguez de Yurre Amato, Angélica Amorim Magalhães, Kelly Grace Mortari, Márcia Renata Medei, Emiliano Horacio Goulart, Jair Trapé Bem, Andreza Fabro de
metadata.dc.contributor.affiliation:	University of Brasilia, Biology Institute, Department of Physiological Sciences, Laboratory of Bioenergetics and Metabolism University of Brasilia, Biology Institute, Department of Physiological Sciences, Laboratory of Bioenergetics and Metabolism University of Brasilia, School of Health Sciences, Laboratory of Molecular Pharmacology University of Brasilia, Biology Institute, Department of Physiological Sciences, Laboratory of Bioenergetics and Metabolism University of Brasilia, Biology Institute, Department of Physiological Sciences, Laboratory of Bioenergetics and Metabolism University of Brasilia, Biology Institute, Department of Physiological Sciences, Laboratory of Bioenergetics and Metabolism University of Brasilia, School of Health Sciences, Laboratory of Molecular Pharmacology Federal University of Rio de Janeiro, Carlos Chagas Filho Institute of Biophysics, Laboratory of Cardioimunology University of Brasilia, School of Health Sciences, Laboratory of Molecular Pharmacology University of Brasilia, Biology Institute, Department of Physiological Sciences, Laboratory of Immunology and Inflammation University of Brasilia,Biology Institute, Department of Physiological Sciences, Laboratory of Neuropharmacology Federal University of Rio de Janeiro, Carlos Chagas Filho Institute of Biophysics, Laboratory of Cardioimunology University of Brasilia, Biology Institute, Department of Physiological Sciences, Laboratory of Bioenergetics and Metabolism University of Brasilia, Biology Institute, Department of Physiological Sciences, Laboratory of Bioenergetics and Metabolism University of Brasilia
Assunto::	Dieta hiperlipídica Estreptozotocina Mitocôndria Hipocampo Tecido adiposo marrom Cognição
Issue Date:	2023
Publisher:	Elsevier Inc.
Citation:	VILELA, Wembley Rodrigues et al. Early-life metabolic dysfunction impairs cognition and mitochondrial function in mice. The Journal of Nutritional Biochemistry, v. 117, 109352, jul. 2023. DOI: https://doi.org/10.1016/j.jnutbio.2023.109352.
Abstract:	The impact of overnutrition early in life is not restricted to the onset of cardiovascular and metabolic diseases, but also affects critical brain functions related to cognition. This study aimed to evaluate the relationship between peripheral metabolic and bioenergetic changes induced by a two-hit protocol and their impact on cognitive function in juvenile mice. Three-week-old male C57BL/6 mice received a high-fat diet (HFD) or control diet for 7 weeks, as sociated with two low doses of streptozotocin (STZ) or vehicle. Despite the absence of obesity, HFD+STZ impaired glucose metabolism and induced a trend towards cholesterol increase. The two-hit protocol impaired recognition and spatial memories in juvenile mice, without inducing a depressive-like behavior. HFD+STZ mice presented increased immunoreactivity for GFAP and a trend towards a decrease in NeuN in the hippocampus. The treatment caused a bioen ergetic impairment in the hippocampus, characterized by a decrease in both O2 consumption related to ATP production and in the maximum respiratory capacity. The thermogenic capacity of brown adipose tissue was impaired by the two-hit protocol, here verified through the absence of a decrease in O2 consumption after uncoupled protein-1 inhibition and an increase in the reserve respiratory capacity. Impaired mitochondrial function was also observed in the liver of HFD+STZ juvenile mice, but not in their heart. These results indicate that exposure to HFD+STZ early in life has a detrimental impact on the bioenergetic and mitochondrial function of tissues with metabolic and thermogenic activities, which is likely related to hippocampal metabolic changes and cognitive impairment.
metadata.dc.description.unidade:	Instituto de Ciências Biológicas (IB) Departamento de Ciências Fisiológicas (IB CFS) Faculdade de Ciências da Saúde (FS) Departamento de Farmácia (FS FAR)
DOI:	https://doi.org/10.1016/j.jnutbio.2023.109352
metadata.dc.relation.publisherversion:	https://www.sciencedirect.com/science/article/pii/S0955286323000852?via%3Dihub
Appears in Collections:	Artigos publicados em periódicos e afins

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