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

PLoS One

Katrina J. Llewellyn¹  Christopher Nguyen¹  Baichang Tan¹  Lbachir BenMohamed¹  Angèle Nalbandian²  Virginia E. Kimonis³  Naomi Walker⁴ 

[1] Department of Pediatrics, Division of Genetics and Genomics Medicine, University of California Irvine, Irvine, CA, 92697, United States of America;Institute for Immunology, University of California Irvine, School of Medicine, Irvine, CA, 92697, United States of America;Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, 92697, United States of America;Sue and Bill Gross Stem Institute, University of California Irvine, Irvine, CA, 92697, United States of America

关键词: Diet;    Lipids;    Mouse models;    Autophagic cell death;    Lysosomes;    Muscle proteins;    Histology;    Lipid analysis;   

DOI  :  10.1371/journal.pone.0131995

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY