title: A Fine Balance of Dietary Lipids Improves Pathology of a Murine Model of VCP-Associated Multisystem Proteinopathy.
abstract: 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.
authors.affiliation: Department of Pediatrics, Division of Genetics and Genomics Medicine, University of California Irvine, Irvine, CA, 92697, United States of America; Sue and Bill Gross Stem Institute, University of California Irvine, Irvine, CA, 92697, United States of America.
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Llewellyn
authors.affiliation: Department of Pediatrics, Division of Genetics and Genomics Medicine, University of California Irvine, Irvine, CA, 92697, United States of America.
authors.forename: Naomi
authors.initials: N
authors.lastname: Walker
authors.affiliation: Department of Pediatrics, Division of Genetics and Genomics Medicine, University of California Irvine, Irvine, CA, 92697, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Nguyen
authors.affiliation: Department of Pediatrics, Division of Genetics and Genomics Medicine, University of California Irvine, Irvine, CA, 92697, United States of America.
authors.forename: Baichang
authors.initials: B
authors.lastname: Tan
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, 92697, United States of America; Institute for Immunology, University of California Irvine, School of Medicine, Irvine, CA, 92697, United States of America.
authors.forename: Lbachir
authors.initials: L
authors.lastname: BenMohamed
authors.affiliation: Department of Pediatrics, Division of Genetics and Genomics Medicine, University of California Irvine, Irvine, CA, 92697, United States of America; Sue and Bill Gross Stem Institute, University of California Irvine, Irvine, CA, 92697, United States of America.
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Kimonis
authors.affiliation: Department of Pediatrics, Division of Genetics and Genomics Medicine, University of California Irvine, Irvine, CA, 92697, United States of America; Sue and Bill Gross Stem Institute, University of California Irvine, Irvine, CA, 92697, United States of America.
authors.forename: Angèle
authors.initials: A
authors.lastname: Nalbandian
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000818:Animals; D001343:Autophagy; D018797:Cell Cycle Proteins / Q000737:chemistry*; D004032:Diet; D004041:Dietary Fats; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D018737:Hand Strength; D006579:Heterozygote; D006706:Homeostasis; D006720:Homozygote; D007150:Immunohistochemistry; D008055:Lipids / Q000737:chemistry*; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000473:pathology; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology*; D015398:Signal Transduction; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D004041:Dietary Fats; D008055:Lipids; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse