Insights into lipid accumulation in skeletal muscle in dysferlin-deficient mice.

Loss of dysferlin protein in humans results in Limb-Girdle Muscular Dystrophy 2B (LGMD2B), characterized by progressive loss of muscles in the distal limbs with impaired locomotion. The Dysferlin null (Bla/J) mouse develops severe steatotic muscles upon aging. Here we report a marked increase in adipocytes, especially in psoas and gluteus, but not in soleus and tibialis anterior muscles in aged Bla/J mice compared to wild type mice. There is a robust upregulation in the mRNA expression of enzymes involved in lipogenesis and triacylglycerol (TAG) synthesis pathways. Lipidomic analysis reveals that the increase in TAG is at the expense of phosphatidylcholine and phosphatidylserine. The adipocytes in steatotic muscles are extra-myocellular, as determined by the increased expression of caveolin1 (a cellular marker for adipocytes) and lipid-droplet protein, perilipin1. This increase in adipocytes occurs as a consequence of the loss of myocytes.