Lipids in Dysferlinopathies
Our laboratory is interested in how lipids associated with ‘Western’ diets can participate to the pathogenesis of dysferlinopathy. Using various genetic models of altered lipid metabolism in combination with dysferlinopathic mice, we are currently studying how muscle fibers respond to changes in circulating lipid and lipoproteins levels, and whether correcting certain plasma lipid parameters can attenuate the rate of decline in muscle function associated with dysferlinopathies.
LGMD2b causes in patients a progressive loss of ambulation. However, despite showing a much milder form of the disease, histological analyses of muscles isolated from rodent models of LGMD2b have revealed characteristic fat-rich fibrofatty infiltrates that help rationalize the minor gait abnormalities behind dysferlin-deficient animals. To highlight the metabolic complications of LGMD2b and how these can play causal roles in the loss of ambulation, this project looked at whether modulation of sterol homeostasis could alter body weight changes, gait abnormalities and muscle morphology of dysferlin-deficient mice.