Metabolomic analyses reveal extensive progenitor cell deficiencies in a mouse model of Duchenne muscular dystrophy

Josiane Joseph, Dong Seong Cho, Jason Doles

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Duchenne muscular dystrophy (DMD) is a musculoskeletal disorder that causes severe morbidity and reduced lifespan. Individuals with DMD have an X-linked mutation that impairs their ability to produce functional dystrophin protein in muscle. No cure exists for this disease and the few therapies that are available do not dramatically delay disease progression. Thus, there is a need to better understand the mechanisms underlying DMD which may ultimately lead to improved treatment options. The muscular dystrophy (MDX) mouse model is frequently used to explore DMD disease traits. Though some studies of metabolism in dystrophic mice exist, few have characterized metabolic profiles of supporting cells in the diseased environment. Using nontargeted metabolomics we characterized metabolic alterations in muscle satellite cells (SCs) and serum of MDX mice. Additionally, live-cell imaging revealed MDX-derived adipose progenitor cell (APC) defects. Finally, metabolomic studies revealed a striking elevation of acylcarnitines in MDX APCs, which we show can inhibit APC proliferation. Together, these studies highlight widespread metabolic alterations in multiple progenitor cell types and serum from MDX mice and implicate dystrophy-associated metabolite imbalances in APCs as a potential contributor to adipose tissue disequilibrium in DMD.

Original languageEnglish (US)
Article number61
JournalMetabolites
Volume8
Issue number4
DOIs
StatePublished - Dec 1 2018

Fingerprint

Metabolomics
Duchenne Muscular Dystrophy
Stem Cells
Muscle
Dystrophin
Cell proliferation
Metabolites
Metabolism
Satellites
Metabolome
Tissue
Muscle Proteins
Muscular Dystrophies
Imaging techniques
Muscular Diseases
Defects
Serum
Muscle Cells
Disease Progression
Adipose Tissue

Keywords

  • Adipose tissue
  • Duchenne muscular dystrophy
  • Metabolomics
  • Skeletal muscle
  • Stem cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology

Cite this

Metabolomic analyses reveal extensive progenitor cell deficiencies in a mouse model of Duchenne muscular dystrophy. / Joseph, Josiane; Cho, Dong Seong; Doles, Jason.

In: Metabolites, Vol. 8, No. 4, 61, 01.12.2018.

Research output: Contribution to journalArticle

@article{a2565af162f6498ba42d64a12aba2ed7,
title = "Metabolomic analyses reveal extensive progenitor cell deficiencies in a mouse model of Duchenne muscular dystrophy",
abstract = "Duchenne muscular dystrophy (DMD) is a musculoskeletal disorder that causes severe morbidity and reduced lifespan. Individuals with DMD have an X-linked mutation that impairs their ability to produce functional dystrophin protein in muscle. No cure exists for this disease and the few therapies that are available do not dramatically delay disease progression. Thus, there is a need to better understand the mechanisms underlying DMD which may ultimately lead to improved treatment options. The muscular dystrophy (MDX) mouse model is frequently used to explore DMD disease traits. Though some studies of metabolism in dystrophic mice exist, few have characterized metabolic profiles of supporting cells in the diseased environment. Using nontargeted metabolomics we characterized metabolic alterations in muscle satellite cells (SCs) and serum of MDX mice. Additionally, live-cell imaging revealed MDX-derived adipose progenitor cell (APC) defects. Finally, metabolomic studies revealed a striking elevation of acylcarnitines in MDX APCs, which we show can inhibit APC proliferation. Together, these studies highlight widespread metabolic alterations in multiple progenitor cell types and serum from MDX mice and implicate dystrophy-associated metabolite imbalances in APCs as a potential contributor to adipose tissue disequilibrium in DMD.",
keywords = "Adipose tissue, Duchenne muscular dystrophy, Metabolomics, Skeletal muscle, Stem cells",
author = "Josiane Joseph and Cho, {Dong Seong} and Jason Doles",
year = "2018",
month = "12",
day = "1",
doi = "10.3390/metabo8040061",
language = "English (US)",
volume = "8",
journal = "Metabolites",
issn = "2218-1989",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "4",

}

TY - JOUR

T1 - Metabolomic analyses reveal extensive progenitor cell deficiencies in a mouse model of Duchenne muscular dystrophy

AU - Joseph, Josiane

AU - Cho, Dong Seong

AU - Doles, Jason

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Duchenne muscular dystrophy (DMD) is a musculoskeletal disorder that causes severe morbidity and reduced lifespan. Individuals with DMD have an X-linked mutation that impairs their ability to produce functional dystrophin protein in muscle. No cure exists for this disease and the few therapies that are available do not dramatically delay disease progression. Thus, there is a need to better understand the mechanisms underlying DMD which may ultimately lead to improved treatment options. The muscular dystrophy (MDX) mouse model is frequently used to explore DMD disease traits. Though some studies of metabolism in dystrophic mice exist, few have characterized metabolic profiles of supporting cells in the diseased environment. Using nontargeted metabolomics we characterized metabolic alterations in muscle satellite cells (SCs) and serum of MDX mice. Additionally, live-cell imaging revealed MDX-derived adipose progenitor cell (APC) defects. Finally, metabolomic studies revealed a striking elevation of acylcarnitines in MDX APCs, which we show can inhibit APC proliferation. Together, these studies highlight widespread metabolic alterations in multiple progenitor cell types and serum from MDX mice and implicate dystrophy-associated metabolite imbalances in APCs as a potential contributor to adipose tissue disequilibrium in DMD.

AB - Duchenne muscular dystrophy (DMD) is a musculoskeletal disorder that causes severe morbidity and reduced lifespan. Individuals with DMD have an X-linked mutation that impairs their ability to produce functional dystrophin protein in muscle. No cure exists for this disease and the few therapies that are available do not dramatically delay disease progression. Thus, there is a need to better understand the mechanisms underlying DMD which may ultimately lead to improved treatment options. The muscular dystrophy (MDX) mouse model is frequently used to explore DMD disease traits. Though some studies of metabolism in dystrophic mice exist, few have characterized metabolic profiles of supporting cells in the diseased environment. Using nontargeted metabolomics we characterized metabolic alterations in muscle satellite cells (SCs) and serum of MDX mice. Additionally, live-cell imaging revealed MDX-derived adipose progenitor cell (APC) defects. Finally, metabolomic studies revealed a striking elevation of acylcarnitines in MDX APCs, which we show can inhibit APC proliferation. Together, these studies highlight widespread metabolic alterations in multiple progenitor cell types and serum from MDX mice and implicate dystrophy-associated metabolite imbalances in APCs as a potential contributor to adipose tissue disequilibrium in DMD.

KW - Adipose tissue

KW - Duchenne muscular dystrophy

KW - Metabolomics

KW - Skeletal muscle

KW - Stem cells

UR - http://www.scopus.com/inward/record.url?scp=85054719358&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054719358&partnerID=8YFLogxK

U2 - 10.3390/metabo8040061

DO - 10.3390/metabo8040061

M3 - Article

AN - SCOPUS:85054719358

VL - 8

JO - Metabolites

JF - Metabolites

SN - 2218-1989

IS - 4

M1 - 61

ER -