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Lipid accumulation in dysferlin-deficient muscles

Item Type:Article
Title:Lipid accumulation in dysferlin-deficient muscles
Creators Name:Grounds, M.D. and Terrill, J. and Radley-Crabb, H. and Robertson, T. and Papadimitriou, J. and Spuler, S. and Shavlakadze, T.
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-{delta}, 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.
Keywords:Adipocytes, Distal Myopathies, Knockout Mice, Limb-Girdle Muscular Dystrophies, Lipid Metabolism, Membrane Proteins, Muscle Proteins, Muscular Atrophy, Skeletal Muscle, Animals, Mice
Source:American Journal of Pathology
ISSN:0002-9440
Publisher:Elsevier (U.S.A.)
Volume:184
Number:6
Page Range:1668-1676
Date:June 2014
Official Publication:https://doi.org/10.1016/j.ajpath.2014.02.005
PubMed:View item in PubMed

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