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The disassembly of the neuromuscular synapse in high-fat diet-induced obese male mice

OBJECTIVE: A sustained high fat diet in mice mimics many features of human obesity. We used male and female Non-Swiss albino mice to investigate the impact of short and long-term high-fat diet-(HFD)-induced obesity on the peripheral neuromuscular junction (NMJ) and whether obesity-related synaptic s...

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Autores principales: Martinez-Pena y Valenzuela, Isabel, Akaaboune, Mohammed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182767/
https://www.ncbi.nlm.nih.gov/pubmed/32283080
http://dx.doi.org/10.1016/j.molmet.2020.100979
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author Martinez-Pena y Valenzuela, Isabel
Akaaboune, Mohammed
author_facet Martinez-Pena y Valenzuela, Isabel
Akaaboune, Mohammed
author_sort Martinez-Pena y Valenzuela, Isabel
collection PubMed
description OBJECTIVE: A sustained high fat diet in mice mimics many features of human obesity. We used male and female Non-Swiss albino mice to investigate the impact of short and long-term high-fat diet-(HFD)-induced obesity on the peripheral neuromuscular junction (NMJ) and whether obesity-related synaptic structural alterations were reversible after switching obese mice from HFD to a standard fat diet (SD). METHODS: HFD-induced obese and age-matched control mice fed SD were used. We carried out in vivo time lapse imaging to monitor changes of synapses over time, quantitative fluorescence imaging to study the regulation of acetylcholine receptor number and density at neuromuscular junctions, and high resolution confocal microscope to study structural alterations in both the pre- and postsynaptic apparatus. RESULTS: Time-lapse imaging in vivo over a 9 month period revealed that NMJs of HFD obese male mice display a variety of obesity-related structural alterations, including the disappearance of large synaptic areas, significant reduction in the density/number of nicotinic acetylcholine receptor (AChRs), abnormal distribution of AChRs, high turnover rate of AChRs, retraction of axons from lost postsynaptic sites, and partially denervated synapses. The severity of these synaptic alterations is associated with the duration of obesity. However, no substantial alterations were observed at NMJs of age-matched HFD obese female mice or male mice fed with a standard or low fat diet. Intriguingly, when obese male mice were switched from HFD to a standard diet, receptor density and the abnormal pattern of AChR distribution were completely reversed to normal, whereas lost synaptic structures were not restored. CONCLUSIONS: These results show that the obese male mice are more vulnerable than female mice to the impacts of long-term HFD on the NMJ damage and provide evidence that diet restriction can partially reverse obesity-related synaptic changes.
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spelling pubmed-71827672020-04-28 The disassembly of the neuromuscular synapse in high-fat diet-induced obese male mice Martinez-Pena y Valenzuela, Isabel Akaaboune, Mohammed Mol Metab Original Article OBJECTIVE: A sustained high fat diet in mice mimics many features of human obesity. We used male and female Non-Swiss albino mice to investigate the impact of short and long-term high-fat diet-(HFD)-induced obesity on the peripheral neuromuscular junction (NMJ) and whether obesity-related synaptic structural alterations were reversible after switching obese mice from HFD to a standard fat diet (SD). METHODS: HFD-induced obese and age-matched control mice fed SD were used. We carried out in vivo time lapse imaging to monitor changes of synapses over time, quantitative fluorescence imaging to study the regulation of acetylcholine receptor number and density at neuromuscular junctions, and high resolution confocal microscope to study structural alterations in both the pre- and postsynaptic apparatus. RESULTS: Time-lapse imaging in vivo over a 9 month period revealed that NMJs of HFD obese male mice display a variety of obesity-related structural alterations, including the disappearance of large synaptic areas, significant reduction in the density/number of nicotinic acetylcholine receptor (AChRs), abnormal distribution of AChRs, high turnover rate of AChRs, retraction of axons from lost postsynaptic sites, and partially denervated synapses. The severity of these synaptic alterations is associated with the duration of obesity. However, no substantial alterations were observed at NMJs of age-matched HFD obese female mice or male mice fed with a standard or low fat diet. Intriguingly, when obese male mice were switched from HFD to a standard diet, receptor density and the abnormal pattern of AChR distribution were completely reversed to normal, whereas lost synaptic structures were not restored. CONCLUSIONS: These results show that the obese male mice are more vulnerable than female mice to the impacts of long-term HFD on the NMJ damage and provide evidence that diet restriction can partially reverse obesity-related synaptic changes. Elsevier 2020-03-18 /pmc/articles/PMC7182767/ /pubmed/32283080 http://dx.doi.org/10.1016/j.molmet.2020.100979 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Martinez-Pena y Valenzuela, Isabel
Akaaboune, Mohammed
The disassembly of the neuromuscular synapse in high-fat diet-induced obese male mice
title The disassembly of the neuromuscular synapse in high-fat diet-induced obese male mice
title_full The disassembly of the neuromuscular synapse in high-fat diet-induced obese male mice
title_fullStr The disassembly of the neuromuscular synapse in high-fat diet-induced obese male mice
title_full_unstemmed The disassembly of the neuromuscular synapse in high-fat diet-induced obese male mice
title_short The disassembly of the neuromuscular synapse in high-fat diet-induced obese male mice
title_sort disassembly of the neuromuscular synapse in high-fat diet-induced obese male mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182767/
https://www.ncbi.nlm.nih.gov/pubmed/32283080
http://dx.doi.org/10.1016/j.molmet.2020.100979
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