Cargando…
The Cognitive Improvement and Alleviation of Brain Hypermetabolism Caused by FFAR3 Ablation in Tg2576 Mice Is Persistent under Diet-Induced Obesity
Obesity and aging are becoming increasingly prevalent across the globe. It has been established that aging is the major risk factor for Alzheimer’s disease (AD), and it is becoming increasingly evident that obesity and the associated insulin resistance are also notably relevant risk factors. The bio...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654726/ https://www.ncbi.nlm.nih.gov/pubmed/36362376 http://dx.doi.org/10.3390/ijms232113591 |
_version_ | 1784829004676595712 |
---|---|
author | Solas, Maite Zamarbide, Marta Ardanaz, Carlos G. Ramírez, María J. Pérez-Mediavilla, Alberto |
author_facet | Solas, Maite Zamarbide, Marta Ardanaz, Carlos G. Ramírez, María J. Pérez-Mediavilla, Alberto |
author_sort | Solas, Maite |
collection | PubMed |
description | Obesity and aging are becoming increasingly prevalent across the globe. It has been established that aging is the major risk factor for Alzheimer’s disease (AD), and it is becoming increasingly evident that obesity and the associated insulin resistance are also notably relevant risk factors. The biological plausibility of the link between high adiposity, insulin resistance, and dementia is central for understanding AD etiology, and to form bases for prevention efforts to decrease the disease burden. Several studies have demonstrated a strong association between short chain fatty acid receptor FFAR3 and insulin sensitivity. Interestingly, it has been recently established that FFAR3 mRNA levels are increased in early stages of the AD pathology, indicating that FFAR3 could play a key role in AD onset and progression. Indeed, in the present study we demonstrate that the ablation of the Ffar3 gene in Tg2576 mice prevents the development of cognitive deficiencies in advanced stages of the disease. Notably, this cognitive improvement is also maintained upon a severe metabolic challenge such as the exposure to high-fat diet (HFD) feeding. Moreover, FFAR3 deletion restores the brain hypermetabolism displayed by Tg2576 mice. Collectively, these data postulate FFAR3 as a potential novel target for AD. |
format | Online Article Text |
id | pubmed-9654726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96547262022-11-15 The Cognitive Improvement and Alleviation of Brain Hypermetabolism Caused by FFAR3 Ablation in Tg2576 Mice Is Persistent under Diet-Induced Obesity Solas, Maite Zamarbide, Marta Ardanaz, Carlos G. Ramírez, María J. Pérez-Mediavilla, Alberto Int J Mol Sci Article Obesity and aging are becoming increasingly prevalent across the globe. It has been established that aging is the major risk factor for Alzheimer’s disease (AD), and it is becoming increasingly evident that obesity and the associated insulin resistance are also notably relevant risk factors. The biological plausibility of the link between high adiposity, insulin resistance, and dementia is central for understanding AD etiology, and to form bases for prevention efforts to decrease the disease burden. Several studies have demonstrated a strong association between short chain fatty acid receptor FFAR3 and insulin sensitivity. Interestingly, it has been recently established that FFAR3 mRNA levels are increased in early stages of the AD pathology, indicating that FFAR3 could play a key role in AD onset and progression. Indeed, in the present study we demonstrate that the ablation of the Ffar3 gene in Tg2576 mice prevents the development of cognitive deficiencies in advanced stages of the disease. Notably, this cognitive improvement is also maintained upon a severe metabolic challenge such as the exposure to high-fat diet (HFD) feeding. Moreover, FFAR3 deletion restores the brain hypermetabolism displayed by Tg2576 mice. Collectively, these data postulate FFAR3 as a potential novel target for AD. MDPI 2022-11-05 /pmc/articles/PMC9654726/ /pubmed/36362376 http://dx.doi.org/10.3390/ijms232113591 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Solas, Maite Zamarbide, Marta Ardanaz, Carlos G. Ramírez, María J. Pérez-Mediavilla, Alberto The Cognitive Improvement and Alleviation of Brain Hypermetabolism Caused by FFAR3 Ablation in Tg2576 Mice Is Persistent under Diet-Induced Obesity |
title | The Cognitive Improvement and Alleviation of Brain Hypermetabolism Caused by FFAR3 Ablation in Tg2576 Mice Is Persistent under Diet-Induced Obesity |
title_full | The Cognitive Improvement and Alleviation of Brain Hypermetabolism Caused by FFAR3 Ablation in Tg2576 Mice Is Persistent under Diet-Induced Obesity |
title_fullStr | The Cognitive Improvement and Alleviation of Brain Hypermetabolism Caused by FFAR3 Ablation in Tg2576 Mice Is Persistent under Diet-Induced Obesity |
title_full_unstemmed | The Cognitive Improvement and Alleviation of Brain Hypermetabolism Caused by FFAR3 Ablation in Tg2576 Mice Is Persistent under Diet-Induced Obesity |
title_short | The Cognitive Improvement and Alleviation of Brain Hypermetabolism Caused by FFAR3 Ablation in Tg2576 Mice Is Persistent under Diet-Induced Obesity |
title_sort | cognitive improvement and alleviation of brain hypermetabolism caused by ffar3 ablation in tg2576 mice is persistent under diet-induced obesity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654726/ https://www.ncbi.nlm.nih.gov/pubmed/36362376 http://dx.doi.org/10.3390/ijms232113591 |
work_keys_str_mv | AT solasmaite thecognitiveimprovementandalleviationofbrainhypermetabolismcausedbyffar3ablationintg2576miceispersistentunderdietinducedobesity AT zamarbidemarta thecognitiveimprovementandalleviationofbrainhypermetabolismcausedbyffar3ablationintg2576miceispersistentunderdietinducedobesity AT ardanazcarlosg thecognitiveimprovementandalleviationofbrainhypermetabolismcausedbyffar3ablationintg2576miceispersistentunderdietinducedobesity AT ramirezmariaj thecognitiveimprovementandalleviationofbrainhypermetabolismcausedbyffar3ablationintg2576miceispersistentunderdietinducedobesity AT perezmediavillaalberto thecognitiveimprovementandalleviationofbrainhypermetabolismcausedbyffar3ablationintg2576miceispersistentunderdietinducedobesity AT solasmaite cognitiveimprovementandalleviationofbrainhypermetabolismcausedbyffar3ablationintg2576miceispersistentunderdietinducedobesity AT zamarbidemarta cognitiveimprovementandalleviationofbrainhypermetabolismcausedbyffar3ablationintg2576miceispersistentunderdietinducedobesity AT ardanazcarlosg cognitiveimprovementandalleviationofbrainhypermetabolismcausedbyffar3ablationintg2576miceispersistentunderdietinducedobesity AT ramirezmariaj cognitiveimprovementandalleviationofbrainhypermetabolismcausedbyffar3ablationintg2576miceispersistentunderdietinducedobesity AT perezmediavillaalberto cognitiveimprovementandalleviationofbrainhypermetabolismcausedbyffar3ablationintg2576miceispersistentunderdietinducedobesity |