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Metabolic dysfunction induced by HFD + L-NAME preferentially affects hippocampal mitochondria, impacting spatial memory in rats

Vilela, Wembley R. LU orcid ; Ramalho, Lisley S. ; Bechara, Luiz R.G. ; Cabral-Costa, João V. ; Serna, Julian D.C. ; Kowaltowski, Alicia J. ; Xavier, Gilberto F. ; Ferreira, Julio C.B. and de Bem, Andreza Fabro (2024) In Journal of Bioenergetics and Biomembranes
Abstract

High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O2) consumption related to ATP production,... (More)

High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O2) consumption related to ATP production, with no changes in H2O2 production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD + L-NAME rats, with no alterations in other morphology-related proteins. Consistently, HFD + L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H2O2 production. Calcium uptake rate and retention capacity in the neocortex of HFD + L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning, whereas neocortical function remains unaffected.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Bioenergetics, Cognition, Hippocampus, Metabolic dysfunction, Mitochondria, Neocortex
in
Journal of Bioenergetics and Biomembranes
publisher
Springer
external identifiers
  • pmid:38374292
  • scopus:85185309077
ISSN
0145-479X
DOI
10.1007/s10863-024-10005-2
language
English
LU publication?
yes
id
c69cc986-ad29-4073-bf25-4f97e743c74d
date added to LUP
2024-03-18 14:18:50
date last changed
2024-04-15 11:41:07
@article{c69cc986-ad29-4073-bf25-4f97e743c74d,
  abstract     = {{<p>High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O<sub>2</sub>) consumption related to ATP production, with no changes in H<sub>2</sub>O<sub>2</sub> production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD + L-NAME rats, with no alterations in other morphology-related proteins. Consistently, HFD + L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H<sub>2</sub>O<sub>2</sub> production. Calcium uptake rate and retention capacity in the neocortex of HFD + L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning, whereas neocortical function remains unaffected.</p>}},
  author       = {{Vilela, Wembley R. and Ramalho, Lisley S. and Bechara, Luiz R.G. and Cabral-Costa, João V. and Serna, Julian D.C. and Kowaltowski, Alicia J. and Xavier, Gilberto F. and Ferreira, Julio C.B. and de Bem, Andreza Fabro}},
  issn         = {{0145-479X}},
  keywords     = {{Bioenergetics; Cognition; Hippocampus; Metabolic dysfunction; Mitochondria; Neocortex}},
  language     = {{eng}},
  publisher    = {{Springer}},
  series       = {{Journal of Bioenergetics and Biomembranes}},
  title        = {{Metabolic dysfunction induced by HFD + L-NAME preferentially affects hippocampal mitochondria, impacting spatial memory in rats}},
  url          = {{http://dx.doi.org/10.1007/s10863-024-10005-2}},
  doi          = {{10.1007/s10863-024-10005-2}},
  year         = {{2024}},
}