Early-life metabolic dysfunction impairs cognition and mitochondrial function in mice.

Autor: Vilela WR; Laboratory of Bioenergetics and Metabolism, Department of Physiological Sciences, Biology Institute, University of Brasilia, Federal District, Brazil., Bellozi PMQ; Laboratory of Bioenergetics and Metabolism, Department of Physiological Sciences, Biology Institute, University of Brasilia, Federal District, Brazil; Laboratory of Molecular Pharmacology, School of Health Sciences, University of Brasilia, Federal District, Brazil., Picolo VL; Laboratory of Bioenergetics and Metabolism, Department of Physiological Sciences, Biology Institute, University of Brasilia, Federal District, Brazil., Cavadas BN; Laboratory of Bioenergetics and Metabolism, Department of Physiological Sciences, Biology Institute, University of Brasilia, Federal District, Brazil., Marques KVS; Laboratory of Bioenergetics and Metabolism, Department of Physiological Sciences, Biology Institute, University of Brasilia, Federal District, Brazil., Pereira LTG; Laboratory of Molecular Pharmacology, School of Health Sciences, University of Brasilia, Federal District, Brazil., Guirao ARY; Laboratory of Cardioimunology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Amato AA; Laboratory of Molecular Pharmacology, School of Health Sciences, University of Brasilia, Federal District, Brazil., Magalhães KG; Laboratory of Immunology and Inflammation, Department of Physiological Sciences, Biology Institute, University of Brasilia, Federal District, Brazil., Mortari MR; Laboratory of Neuropharmacology, Department of Physiological Sciences, Biology Institute, University of Brasilia, Federal District, Brazil., Medei EH; Laboratory of Cardioimunology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Goulart JT; Laboratory of Bioenergetics and Metabolism, Department of Physiological Sciences, Biology Institute, University of Brasilia, Federal District, Brazil. Electronic address: jair.goulart@unb.br., de Bem AF; Laboratory of Bioenergetics and Metabolism, Department of Physiological Sciences, Biology Institute, University of Brasilia, Federal District, Brazil; Center of Social and Affective Neuroscience, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health, Linköping University, Linköping, Sweden; National Institute of Science and Technology on Neuroimmunomodulation, Rio de Janeiro, Brazil.. Electronic address: debemandreza@gmail.com.
Jazyk: angličtina
Zdroj: The Journal of nutritional biochemistry [J Nutr Biochem] 2023 Jul; Vol. 117, pp. 109352. Date of Electronic Publication: 2023 Apr 14.
DOI: 10.1016/j.jnutbio.2023.109352
Abstrakt: 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, associated 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 bioenergetic impairment in the hippocampus, characterized by a decrease in both O 2 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 O 2 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.
Competing Interests: Declaration of competing Interest The authors declare that they have no other competing financial interests or personal relationships that could have influenced this work.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: