PloS one

A Fine Balance of Dietary Lipids Improves Pathology of a Murine Model of VCP-Associated Multisystem Proteinopathy.

PMID 26134519


The discovery of effective therapies and of disease mechanisms underlying valosin containing protein (VCP)-associated myopathies and neurodegenerative disorders remains elusive. VCP disease, caused by mutations in the VCP gene, are a clinically and genetically heterogeneous group of disorders with manifestations varying from hereditary inclusion body myopathy, Paget's disease of bone, frontotemporal dementia (IBMPFD), and amyotrophic lateral sclerosis (ALS). In the present study, we examined the effects of higher dietary lipid percentages on VCPR155H/R155H, VCPR155H/+ and Wild Type (WT) mice from birth until 15 months of age by immunohistochemical and biochemical assays. Findings illustrated improvement in the muscle strength, histology, and autophagy signaling pathway in the heterozygote mice when fed 9% lipid-enriched diets (LED). However, increasing the LED by 12%, 30%, and 48% showed no improvement in homozygote and heterozygote survival, muscle pathology, lipid accumulation or the autophagy cascade. These findings suggest that a balanced lipid supplementation may have a therapeutic strategy for patients with VCP-associated multisystem proteinopathies.