CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis
Human mutations in carnitine palmitoyl transferase 1A (CPT1A) are correlated with a remarkably low prevalence of multiple sclerosis (MS) in Inuits (P479L) and Hutterites (G710E). To elucidate the role of CPT1A, we established a Cpt1a P479L mouse strain and evaluated its sensitivity to experimental a...
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2019
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Online Access: | https://vbn.aau.dk/da/publications/a77c1195-cbf3-4386-86bc-6b1fd4970573 https://doi.org/10.1038/s41598-019-49868-6 https://vbn.aau.dk/ws/files/311243228/s41598_019_49868_6.pdf http://www.scopus.com/inward/record.url?scp=85072304468&partnerID=8YFLogxK |
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ftalborgunivpubl:oai:pure.atira.dk:publications/a77c1195-cbf3-4386-86bc-6b1fd4970573 2024-05-12T08:06:11+00:00 CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis Mørkholt, Anne Skøttrup Trabjerg, Michael Sloth Oklinski, Michal Krystian Egelund Bolther, Luise Kroese, Lona John Pritchard, Colin Eliot Jason Huijbers, Ivo Johan Nieland, John Dirk Vestergaard 2019-09-16 application/pdf https://vbn.aau.dk/da/publications/a77c1195-cbf3-4386-86bc-6b1fd4970573 https://doi.org/10.1038/s41598-019-49868-6 https://vbn.aau.dk/ws/files/311243228/s41598_019_49868_6.pdf http://www.scopus.com/inward/record.url?scp=85072304468&partnerID=8YFLogxK eng eng https://vbn.aau.dk/da/publications/a77c1195-cbf3-4386-86bc-6b1fd4970573 info:eu-repo/semantics/openAccess Mørkholt , A S , Trabjerg , M S , Oklinski , M K E , Bolther , L , Kroese , L J , Pritchard , C E J , Huijbers , I J & Nieland , J D V 2019 , ' CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis ' , Scientific Reports , vol. 9 , no. 1 , 13299 . https://doi.org/10.1038/s41598-019-49868-6 article 2019 ftalborgunivpubl https://doi.org/10.1038/s41598-019-49868-6 2024-04-15T00:50:54Z Human mutations in carnitine palmitoyl transferase 1A (CPT1A) are correlated with a remarkably low prevalence of multiple sclerosis (MS) in Inuits (P479L) and Hutterites (G710E). To elucidate the role of CPT1A, we established a Cpt1a P479L mouse strain and evaluated its sensitivity to experimental autoimmune encephalomyelitis (EAE) induction. Since CPT1a is a key molecule in lipid metabolism, we compared the effects of a high-fat diet (HFD) and normal diet (ND) on disease progression. The disease severity increased significantly in WT mice compared to that in Cpt1 P479L mice. In addition, WT mice receiving HFD showed markedly exacerbated disease course when compared either with Cpt1a P479L mice receiving HFD or WT control group receiving ND. Induction of EAE caused a significant decrease of myelin basic protein expression in the hindbrain of disease affected WT mice in comparison to Cpt1a P479L mice. Further, WT mice showed increased expression of oxidative stress markers like Nox2 and Ho-1, whereas expression of mitochondrial antioxidants regulator Pgc1α was increased in Cpt1a P479L mice. Our results suggest that, lipids metabolism play an important role in EAE, as shown by the higher severity of disease progression in both WT EAE and WT EAF HFD-fed mice in contrast to their counterpart Cpt1a P479L mutant mice. Interestingly, mice with downregulated lipid metabolism due to the Cpt1a P479L mutation showed resistance to EAE induction. These findings support a key role for CPT1A in the development of EAE and could be a promising target in MS treatment. Article in Journal/Newspaper inuits Aalborg University's Research Portal Scientific Reports 9 1 |
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Aalborg University's Research Portal |
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description |
Human mutations in carnitine palmitoyl transferase 1A (CPT1A) are correlated with a remarkably low prevalence of multiple sclerosis (MS) in Inuits (P479L) and Hutterites (G710E). To elucidate the role of CPT1A, we established a Cpt1a P479L mouse strain and evaluated its sensitivity to experimental autoimmune encephalomyelitis (EAE) induction. Since CPT1a is a key molecule in lipid metabolism, we compared the effects of a high-fat diet (HFD) and normal diet (ND) on disease progression. The disease severity increased significantly in WT mice compared to that in Cpt1 P479L mice. In addition, WT mice receiving HFD showed markedly exacerbated disease course when compared either with Cpt1a P479L mice receiving HFD or WT control group receiving ND. Induction of EAE caused a significant decrease of myelin basic protein expression in the hindbrain of disease affected WT mice in comparison to Cpt1a P479L mice. Further, WT mice showed increased expression of oxidative stress markers like Nox2 and Ho-1, whereas expression of mitochondrial antioxidants regulator Pgc1α was increased in Cpt1a P479L mice. Our results suggest that, lipids metabolism play an important role in EAE, as shown by the higher severity of disease progression in both WT EAE and WT EAF HFD-fed mice in contrast to their counterpart Cpt1a P479L mutant mice. Interestingly, mice with downregulated lipid metabolism due to the Cpt1a P479L mutation showed resistance to EAE induction. These findings support a key role for CPT1A in the development of EAE and could be a promising target in MS treatment. |
format |
Article in Journal/Newspaper |
author |
Mørkholt, Anne Skøttrup Trabjerg, Michael Sloth Oklinski, Michal Krystian Egelund Bolther, Luise Kroese, Lona John Pritchard, Colin Eliot Jason Huijbers, Ivo Johan Nieland, John Dirk Vestergaard |
spellingShingle |
Mørkholt, Anne Skøttrup Trabjerg, Michael Sloth Oklinski, Michal Krystian Egelund Bolther, Luise Kroese, Lona John Pritchard, Colin Eliot Jason Huijbers, Ivo Johan Nieland, John Dirk Vestergaard CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis |
author_facet |
Mørkholt, Anne Skøttrup Trabjerg, Michael Sloth Oklinski, Michal Krystian Egelund Bolther, Luise Kroese, Lona John Pritchard, Colin Eliot Jason Huijbers, Ivo Johan Nieland, John Dirk Vestergaard |
author_sort |
Mørkholt, Anne Skøttrup |
title |
CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis |
title_short |
CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis |
title_full |
CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis |
title_fullStr |
CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis |
title_full_unstemmed |
CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis |
title_sort |
cpt1a plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis |
publishDate |
2019 |
url |
https://vbn.aau.dk/da/publications/a77c1195-cbf3-4386-86bc-6b1fd4970573 https://doi.org/10.1038/s41598-019-49868-6 https://vbn.aau.dk/ws/files/311243228/s41598_019_49868_6.pdf http://www.scopus.com/inward/record.url?scp=85072304468&partnerID=8YFLogxK |
genre |
inuits |
genre_facet |
inuits |
op_source |
Mørkholt , A S , Trabjerg , M S , Oklinski , M K E , Bolther , L , Kroese , L J , Pritchard , C E J , Huijbers , I J & Nieland , J D V 2019 , ' CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis ' , Scientific Reports , vol. 9 , no. 1 , 13299 . https://doi.org/10.1038/s41598-019-49868-6 |
op_relation |
https://vbn.aau.dk/da/publications/a77c1195-cbf3-4386-86bc-6b1fd4970573 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1038/s41598-019-49868-6 |
container_title |
Scientific Reports |
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9 |
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1 |
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1798848635050393600 |