title: Lipolysis and lipophagy in lipid storage myopathies.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Fondazione San Camillo Hospital IRCCS, via Alberoni 70, 30126 Lido Venice, Italy. Electronic address: corrado.angelini@unipd.it.
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.affiliation: Department of Neurosciences, University of Padova, via Giustiniani 5, 35128 Padova, Italy.
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Nascimbeni
authors.affiliation: Department of Radiological and Histopathological Sciences, Alma Mater University of Bologna, via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cenacchi
authors.affiliation: Fondazione San Camillo Hospital IRCCS, via Alberoni 70, 30126 Lido Venice, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Tasca
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001343:Autophagy; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology*; D002331:Carnitine / Q000172:deficiency* / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency* / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000378:metabolism / Q000473:pathology*; D008052:Lipid Metabolism, Inborn Errors / Q000378:metabolism / Q000473:pathology*; D008066:Lipolysis; D008297:Male; D008661:Metabolism, Inborn Errors / Q000378:metabolism / Q000473:pathology*; D054069:Multiple Acyl Coenzyme A Dehydrogenase Deficiency / Q000378:metabolism / Q000473:pathology*; D009132:Muscles / Q000378:metabolism / Q000473:pathology*; D009135:Muscular Diseases / Q000378:metabolism / Q000473:pathology*; D009136:Muscular Dystrophies / Q000378:metabolism / Q000473:pathology*
chemical_list: D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine
keywords: Carnitine deficiency; Lipid storage myopathy; MADD; NLSD-M; TFEB