Abstract
Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder leading to paralysis and subsequent death in young children. Initially considered a motor neuron disease, extra‐neuronal involvement is increasingly recognized. The primary goal of this study was to investigate alterations in lipid metabolism in SMA patients and mouse models of the disease.
Methods
We analyzed clinical data collected from a large cohort of pediatric SMA type I–III patients as well as SMA type I liver necropsy data. In parallel, we performed histology, lipid analysis, and transcript profiling in mouse models of SMA.
Results
We identify an increased susceptibility to developing dyslipidemia in a cohort of 72 SMA patients and liver steatosis in pathological samples. Similarly, fatty acid metabolic abnormalities were present in all SMA mouse models studied. Specifically, Smn2B/‐ mice displayed elevated hepatic triglycerides and dyslipidemia, resembling non‐alcoholic fatty liver disease (NAFLD). Interestingly, this phenotype appeared prior to denervation.
Interpretation
This work highlights metabolic abnormalities as an important feature of SMA, suggesting implementation of nutritional and screening guidelines in patients, as such defects are likely to increase metabolic distress and cardiovascular risk. This study emphasizes the need for a systemic therapeutic approach to ensure maximal benefits for all SMA patients throughout their life.
| Original language | English |
|---|---|
| Pages (from-to) | 1519-1532 |
| Number of pages | 14 |
| Journal | Annals of Clinical and Translational Neurology |
| Volume | 6 |
| Issue number | 8 |
| Early online date | 26 Jul 2019 |
| DOIs | |
| Publication status | Published - Aug 2019 |
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Keywords
- MOTOR-NEURON PROTEIN
- GLUCOSE-METABOLISM
- INTRINSIC DEFECTS
- CARDIAC DEFECTS
- MOUSE MODEL
- PREVALENCE
- CHILDREN
- LIVER
- DYSLIPIDEMIA
- ADOLESCENTS
Cite this
Abnormal fatty acid metabolism is a core component of spinal muscular atrophy. / Deguise, Marc‐Olivier; Baranello, Giovanni; Mastella, Chiara; Beauvais , Ariane; Michaud, Jean; Leone, Alessandro; De Amicis, Ramona; Battezzati, Alberto; Dunham, Christopher; Selby, Kathryn; Chardon, Jodi Warman; McMillan, Hugh J.; Huang, Yu‐Ting; Courtney, Natalie L.; Mole, Alannah J.; Kubinski, Sabrina; Claus, Peter; Murray, Lyndsay M.; Bowerman, Melissa; Gillingwater, Thomas H.; Bertoli, Simona; Parson, Simon H.; Kothary, Rashmi (Corresponding Author).
In: Annals of Clinical and Translational Neurology, Vol. 6, No. 8, 08.2019, p. 1519-1532.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Abnormal fatty acid metabolism is a core component of spinal muscular atrophy
AU - Deguise, Marc‐Olivier
AU - Baranello, Giovanni
AU - Mastella, Chiara
AU - Beauvais , Ariane
AU - Michaud, Jean
AU - Leone, Alessandro
AU - De Amicis, Ramona
AU - Battezzati, Alberto
AU - Dunham, Christopher
AU - Selby, Kathryn
AU - Chardon, Jodi Warman
AU - McMillan, Hugh J.
AU - Huang, Yu‐Ting
AU - Courtney, Natalie L.
AU - Mole, Alannah J.
AU - Kubinski, Sabrina
AU - Claus, Peter
AU - Murray, Lyndsay M.
AU - Bowerman, Melissa
AU - Gillingwater, Thomas H.
AU - Bertoli, Simona
AU - Parson, Simon H.
AU - Kothary, Rashmi
N1 - © 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
PY - 2019/8
Y1 - 2019/8
N2 - ObjectiveSpinal muscular atrophy (SMA) is an inherited neuromuscular disorder leading to paralysis and subsequent death in young children. Initially considered a motor neuron disease, extra‐neuronal involvement is increasingly recognized. The primary goal of this study was to investigate alterations in lipid metabolism in SMA patients and mouse models of the disease.MethodsWe analyzed clinical data collected from a large cohort of pediatric SMA type I–III patients as well as SMA type I liver necropsy data. In parallel, we performed histology, lipid analysis, and transcript profiling in mouse models of SMA.ResultsWe identify an increased susceptibility to developing dyslipidemia in a cohort of 72 SMA patients and liver steatosis in pathological samples. Similarly, fatty acid metabolic abnormalities were present in all SMA mouse models studied. Specifically, Smn2B/‐ mice displayed elevated hepatic triglycerides and dyslipidemia, resembling non‐alcoholic fatty liver disease (NAFLD). Interestingly, this phenotype appeared prior to denervation.InterpretationThis work highlights metabolic abnormalities as an important feature of SMA, suggesting implementation of nutritional and screening guidelines in patients, as such defects are likely to increase metabolic distress and cardiovascular risk. This study emphasizes the need for a systemic therapeutic approach to ensure maximal benefits for all SMA patients throughout their life.
AB - ObjectiveSpinal muscular atrophy (SMA) is an inherited neuromuscular disorder leading to paralysis and subsequent death in young children. Initially considered a motor neuron disease, extra‐neuronal involvement is increasingly recognized. The primary goal of this study was to investigate alterations in lipid metabolism in SMA patients and mouse models of the disease.MethodsWe analyzed clinical data collected from a large cohort of pediatric SMA type I–III patients as well as SMA type I liver necropsy data. In parallel, we performed histology, lipid analysis, and transcript profiling in mouse models of SMA.ResultsWe identify an increased susceptibility to developing dyslipidemia in a cohort of 72 SMA patients and liver steatosis in pathological samples. Similarly, fatty acid metabolic abnormalities were present in all SMA mouse models studied. Specifically, Smn2B/‐ mice displayed elevated hepatic triglycerides and dyslipidemia, resembling non‐alcoholic fatty liver disease (NAFLD). Interestingly, this phenotype appeared prior to denervation.InterpretationThis work highlights metabolic abnormalities as an important feature of SMA, suggesting implementation of nutritional and screening guidelines in patients, as such defects are likely to increase metabolic distress and cardiovascular risk. This study emphasizes the need for a systemic therapeutic approach to ensure maximal benefits for all SMA patients throughout their life.
KW - MOTOR-NEURON PROTEIN
KW - GLUCOSE-METABOLISM
KW - INTRINSIC DEFECTS
KW - CARDIAC DEFECTS
KW - MOUSE MODEL
KW - PREVALENCE
KW - CHILDREN
KW - LIVER
KW - DYSLIPIDEMIA
KW - ADOLESCENTS
UR - http://www.mendeley.com/research/abnormal-fatty-acid-metabolism-core-component-spinal-muscular-atrophy
U2 - 10.1002/acn3.50855
DO - 10.1002/acn3.50855
M3 - Article
VL - 6
SP - 1519
EP - 1532
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
SN - 2328-9503
IS - 8
ER -