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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...

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Autores principales: Angelini, Corrado, Nascimbeni, Anna Chiara, Cenacchi, Giovanna, Tasca, Elisabetta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Pub. Co 2016
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.
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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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