Obesogenic Diets Cause Alterations on Proteins and Theirs Post-Translational Modifications in Mouse Brains
Siino, Valentina LU ; Jensen, Pia ; James, Peter LU
; Vasto, Sonya
; Amato, Antonella
; Mulè, Flavia
; Accardi, Giulia
and Larsen, Martin Røssel
(2021)
In Nutrition and Metabolic Insights
14.
- Abstract
Obesity constitutes a major global health threat and is associated with a variety of diseases ranging from metabolic and cardiovascular disease, cancer to neurodegeneration. The hallmarks of neurodegeneration include oxidative stress, proteasome impairment, mitochondrial dysfunction and accumulation of abnormal protein aggregates as well as metabolic alterations. As an example, in post-mortem brain of patients with Alzheimer’s disease (AD), several studies have reported reduction of insulin, insulin-like growth factor 1 and insulin receptor and an increase in tau protein and glycogen-synthase kinase-3β compared to healthy controls suggesting an impairment of metabolism in the AD patient’s brain. Given these lines of evidence, in the... (More)
Obesity constitutes a major global health threat and is associated with a variety of diseases ranging from metabolic and cardiovascular disease, cancer to neurodegeneration. The hallmarks of neurodegeneration include oxidative stress, proteasome impairment, mitochondrial dysfunction and accumulation of abnormal protein aggregates as well as metabolic alterations. As an example, in post-mortem brain of patients with Alzheimer’s disease (AD), several studies have reported reduction of insulin, insulin-like growth factor 1 and insulin receptor and an increase in tau protein and glycogen-synthase kinase-3β compared to healthy controls suggesting an impairment of metabolism in the AD patient’s brain. Given these lines of evidence, in the present study we investigated brains of mice treated with 2 obesogenic diets, high-fat diet (HFD) and high-glycaemic diet (HGD), compared to mice fed with a standard diet (SD) employing a quantitative mass spectrometry-based approach. Moreover, post-translational modified proteins (phosphorylated and N-linked glycosylated) were studied. The aim of the study was to identify proteins present in the brain that are changing their expression based on the diet given to the mice. We believed that some of these changes would highlight pathways and molecular mechanisms that could link obesity to brain impairment. The results showed in this study suggest that, together with cytoskeletal proteins, mitochondria and metabolic proteins are changing their post-translational status in brains of obese mice. Specifically, proteins involved in metabolic pathways and in mitochondrial functions are mainly downregulated in mice fed with obesogenic diets compared to SD. These changes suggest a reduced metabolism and a lower activity of mitochondria in obese mice. Some of these proteins, such as PGM1 and MCT1 have been shown to be involved in brain impairment as well. These results might shed light on the well-studied correlation between obesity and brain damage. The results presented here are in agreement with previous findings and aim to open new perspectives on the connection between diet-induced obesity and brain impairment.
(Less)
- author
- Siino, Valentina
LU
; Jensen, Pia
; James, Peter
LU
; Vasto, Sonya
; Amato, Antonella
; Mulè, Flavia
; Accardi, Giulia
and Larsen, Martin Røssel
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- brain impairment, nutrition, Obesity, post-translational modifications, proteomics
- in
- Nutrition and Metabolic Insights
- volume
- 14
- publisher
- SAGE Publications
- external identifiers
-
- pmid:34017182
- scopus:85133321966
- ISSN
- 1178-6388
- DOI
- 10.1177/11786388211012405
- language
- English
- LU publication?
- yes
- id
- c6ddec26-9e3e-4fc5-a0c6-8986b291baf2
- date added to LUP
- 2022-09-23 14:38:43
- date last changed
- 2024-04-15 19:09:46
@article{c6ddec26-9e3e-4fc5-a0c6-8986b291baf2,
abstract = {{<p>Obesity constitutes a major global health threat and is associated with a variety of diseases ranging from metabolic and cardiovascular disease, cancer to neurodegeneration. The hallmarks of neurodegeneration include oxidative stress, proteasome impairment, mitochondrial dysfunction and accumulation of abnormal protein aggregates as well as metabolic alterations. As an example, in post-mortem brain of patients with Alzheimer’s disease (AD), several studies have reported reduction of insulin, insulin-like growth factor 1 and insulin receptor and an increase in tau protein and glycogen-synthase kinase-3β compared to healthy controls suggesting an impairment of metabolism in the AD patient’s brain. Given these lines of evidence, in the present study we investigated brains of mice treated with 2 obesogenic diets, high-fat diet (HFD) and high-glycaemic diet (HGD), compared to mice fed with a standard diet (SD) employing a quantitative mass spectrometry-based approach. Moreover, post-translational modified proteins (phosphorylated and N-linked glycosylated) were studied. The aim of the study was to identify proteins present in the brain that are changing their expression based on the diet given to the mice. We believed that some of these changes would highlight pathways and molecular mechanisms that could link obesity to brain impairment. The results showed in this study suggest that, together with cytoskeletal proteins, mitochondria and metabolic proteins are changing their post-translational status in brains of obese mice. Specifically, proteins involved in metabolic pathways and in mitochondrial functions are mainly downregulated in mice fed with obesogenic diets compared to SD. These changes suggest a reduced metabolism and a lower activity of mitochondria in obese mice. Some of these proteins, such as PGM1 and MCT1 have been shown to be involved in brain impairment as well. These results might shed light on the well-studied correlation between obesity and brain damage. The results presented here are in agreement with previous findings and aim to open new perspectives on the connection between diet-induced obesity and brain impairment.</p>}},
author = {{Siino, Valentina and Jensen, Pia and James, Peter and Vasto, Sonya and Amato, Antonella and Mulè, Flavia and Accardi, Giulia and Larsen, Martin Røssel}},
issn = {{1178-6388}},
keywords = {{brain impairment; nutrition; Obesity; post-translational modifications; proteomics}},
language = {{eng}},
publisher = {{SAGE Publications}},
series = {{Nutrition and Metabolic Insights}},
title = {{Obesogenic Diets Cause Alterations on Proteins and Theirs Post-Translational Modifications in Mouse Brains}},
url = {{http://dx.doi.org/10.1177/11786388211012405}},
doi = {{10.1177/11786388211012405}},
volume = {{14}},
year = {{2021}},
}