Lipolysis and lipophagy in lipid storage myopathies

Biochim Biophys Acta. 2016 Jul;1862(7):1367-73. doi: 10.1016/j.bbadis.2016.04.008. Epub 2016 Apr 13.


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.

Keywords: Carnitine deficiency; Lipid storage myopathy; MADD; NLSD-M; TFEB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autophagy
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / pathology*
  • Carnitine / deficiency*
  • Carnitine / metabolism
  • Carnitine O-Palmitoyltransferase / deficiency*
  • Carnitine O-Palmitoyltransferase / metabolism
  • Child
  • Female
  • Humans
  • Hyperammonemia / metabolism
  • Hyperammonemia / pathology*
  • Lipid Metabolism, Inborn Errors / metabolism
  • Lipid Metabolism, Inborn Errors / pathology*
  • Lipolysis*
  • Male
  • Metabolism, Inborn Errors / metabolism
  • Metabolism, Inborn Errors / pathology*
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency / metabolism
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency / pathology*
  • Muscles / metabolism
  • Muscles / pathology*
  • Muscular Diseases / metabolism
  • Muscular Diseases / pathology*
  • Muscular Dystrophies / metabolism
  • Muscular Dystrophies / pathology*


  • Carnitine O-Palmitoyltransferase
  • Carnitine

Supplementary concepts

  • Carnitine palmitoyl transferase 2 deficiency
  • Myopathy with Abnormal Lipid Metabolism
  • Systemic carnitine deficiency