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Lipolysis and lipophagy in lipid storage myopathies
AIMS: Triglycerides droplets are massively stored in muscle in Lipid Storage Myopathies (LSM). We studied in muscle regulators of lipophagy, the expression of the transcription factor-EB (TFEB) (a master regulator of lysosomal biogenesis), and markers of autophagy which are induced by starvation and...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Pub. Co
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879869/ https://www.ncbi.nlm.nih.gov/pubmed/27085974 http://dx.doi.org/10.1016/j.bbadis.2016.04.008 |
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author | Angelini, Corrado Nascimbeni, Anna Chiara Cenacchi, Giovanna Tasca, Elisabetta |
author_facet | Angelini, Corrado Nascimbeni, Anna Chiara Cenacchi, Giovanna Tasca, Elisabetta |
author_sort | Angelini, Corrado |
collection | PubMed |
description | AIMS: Triglycerides droplets are massively stored in muscle in Lipid Storage Myopathies (LSM). We studied in muscle regulators of lipophagy, the expression of the transcription factor-EB (TFEB) (a master regulator of lysosomal biogenesis), and markers of autophagy which are induced by starvation and exert a transcriptional control on lipid catabolism. METHODS: We investigated the factors that regulate lipophagy in muscle biopsies from 6 patients with different types of LSM: 2 cases of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD), 1 case of primary carnitine deficiency (CD), 2 cases of neutral lipid storage myopathy (NLSD-M), 1 case of carnitine–palmitoyl-transferase-II (CPT) deficiency. RESULTS: Conventional morphology and electron microscopy documented the lipid accumulation and its dramatic resolution after treatment. Muscle immunofluorescence showed that while in MADD and NLSD-M there was a co-localized expression of TFEB and p62-SQSTM1 (marker of protein aggregates) in some atrophic fibers, in CD and CPT-II deficiency the reaction was almost normal. In regenerating fibers, TFEB localized in the cytoplasm (inactive form), whereas in atrophic fibers it localized in the nuclei (active form). Lipid-accumulated/atrophic fibers did not display p62-positive protein aggregates, indicating, together with the LC3-II (marker of autophagosomes) and p62-SQSTM1 analysis, that the autophagic flux is often preserved and lipophagy occurs. CONCLUSION: In atrophic and regenerating fibers of patients with NLSD-M we observed TFEB over-expression; in other conditions autophagy markers are increased, suggesting lipophagy active role on human lipid metabolism. |
format | Online Article Text |
id | pubmed-4879869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier Pub. Co |
record_format | MEDLINE/PubMed |
spelling | pubmed-48798692016-07-01 Lipolysis and lipophagy in lipid storage myopathies Angelini, Corrado Nascimbeni, Anna Chiara Cenacchi, Giovanna Tasca, Elisabetta Biochim Biophys Acta Article AIMS: Triglycerides droplets are massively stored in muscle in Lipid Storage Myopathies (LSM). We studied in muscle regulators of lipophagy, the expression of the transcription factor-EB (TFEB) (a master regulator of lysosomal biogenesis), and markers of autophagy which are induced by starvation and exert a transcriptional control on lipid catabolism. METHODS: We investigated the factors that regulate lipophagy in muscle biopsies from 6 patients with different types of LSM: 2 cases of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD), 1 case of primary carnitine deficiency (CD), 2 cases of neutral lipid storage myopathy (NLSD-M), 1 case of carnitine–palmitoyl-transferase-II (CPT) deficiency. RESULTS: Conventional morphology and electron microscopy documented the lipid accumulation and its dramatic resolution after treatment. Muscle immunofluorescence showed that while in MADD and NLSD-M there was a co-localized expression of TFEB and p62-SQSTM1 (marker of protein aggregates) in some atrophic fibers, in CD and CPT-II deficiency the reaction was almost normal. In regenerating fibers, TFEB localized in the cytoplasm (inactive form), whereas in atrophic fibers it localized in the nuclei (active form). Lipid-accumulated/atrophic fibers did not display p62-positive protein aggregates, indicating, together with the LC3-II (marker of autophagosomes) and p62-SQSTM1 analysis, that the autophagic flux is often preserved and lipophagy occurs. CONCLUSION: In atrophic and regenerating fibers of patients with NLSD-M we observed TFEB over-expression; in other conditions autophagy markers are increased, suggesting lipophagy active role on human lipid metabolism. Elsevier Pub. Co 2016-07 /pmc/articles/PMC4879869/ /pubmed/27085974 http://dx.doi.org/10.1016/j.bbadis.2016.04.008 Text en © 2016 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 | Article Angelini, Corrado Nascimbeni, Anna Chiara Cenacchi, Giovanna Tasca, Elisabetta Lipolysis and lipophagy in lipid storage myopathies |
title | Lipolysis and lipophagy in lipid storage myopathies |
title_full | Lipolysis and lipophagy in lipid storage myopathies |
title_fullStr | Lipolysis and lipophagy in lipid storage myopathies |
title_full_unstemmed | Lipolysis and lipophagy in lipid storage myopathies |
title_short | Lipolysis and lipophagy in lipid storage myopathies |
title_sort | lipolysis and lipophagy in lipid storage myopathies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879869/ https://www.ncbi.nlm.nih.gov/pubmed/27085974 http://dx.doi.org/10.1016/j.bbadis.2016.04.008 |
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