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Am J Pathol. 2014 Jun;184(6):1668-76. doi: 10.1016/j.ajpath.2014.02.005. Epub 2014 Mar 29.

Lipid accumulation in dysferlin-deficient muscles.

Author information

  • 1Schools of Anatomy, Physiology and Human Biology, University of Western Australia, Perth, Australia. Electronic address: miranda.grounds@uwa.edu.au.
  • 2Schools of Anatomy, Physiology and Human Biology, University of Western Australia, Perth, Australia.
  • 3Schools of Anatomy, Physiology and Human Biology, University of Western Australia, Perth, Australia; CHIRI Biosciences Research Precinct, School of Biomedical Sciences, Curtin University, Perth, Australia.
  • 4Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
  • 5Muscle Research Unit, Experimental and Clinical Research Center, Berlin, Germany.

Abstract

Dysferlin is a membrane associated protein involved in vesicle trafficking and fusion. Defects in dysferlin result in limb-girdle muscular dystrophy type 2B and Miyoshi myopathy in humans and myopathy in A/J(dys-/-) and BLAJ mice, but the pathomechanism of the myopathy is not understood. Oil Red O staining showed many lipid droplets within the psoas and quadriceps muscles of dysferlin-deficient A/J(dys-/-) mice aged 8 and 12 months, and lipid droplets were also conspicuous within human myofibers from patients with dysferlinopathy (but not other myopathies). Electron microscopy of 8-month-old A/J(dys-/-) psoas muscles confirmed lipid droplets within myofibers and showed disturbed architecture of myofibers. In addition, the presence of many adipocytes was confirmed, and a possible role for dysferlin in adipocytes is suggested. Increased expression of mRNA for a gene involved in early lipogenesis, CCAAT/enhancer binding protein-δ, in 3-month-old A/J(dys-/-) quadriceps (before marked histopathology is evident), indicates early induction of lipogenesis/adipogenesis within dysferlin-deficient muscles. Similar results were seen for dysferlin-deficient BLAJ mice. These novel observations of conspicuous intermyofibrillar lipid and progressive adipocyte replacement in dysferlin-deficient muscles present a new focus for investigating the mechanisms that result in the progressive decline of muscle function in dysferlinopathies.

Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PMID:
24685690
[PubMed - in process]
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