Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia
Background: Pathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported in this multisystem neurodegenerative disease....
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MDPI AG
2022-11-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/22/4803 |
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| author | Martin Regensburger Laura Krumm Manuel Alexander Schmidt Andreas Schmid Imke Tabea Spatz Dominique Cornelius Marterstock Christoph Kopp Zacharias Kohl Arnd Doerfler Thomas Karrasch Beate Winner Jürgen Winkler |
| author_facet | Martin Regensburger Laura Krumm Manuel Alexander Schmidt Andreas Schmid Imke Tabea Spatz Dominique Cornelius Marterstock Christoph Kopp Zacharias Kohl Arnd Doerfler Thomas Karrasch Beate Winner Jürgen Winkler |
| author_sort | Martin Regensburger |
| collection | DOAJ |
| description | Background: Pathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported in this multisystem neurodegenerative disease. However, a detailed analysis of the metabolic state is lacking. Methods: In order to characterize metabolic alterations, a cross-sectional analysis was performed comparing SPG11 patients (n = 16) and matched healthy controls (n = 16). We quantified anthropometric parameters, body composition as determined by bioimpedance spectroscopy, and serum metabolic biomarkers, and we measured hypothalamic volume by high-field MRI. Results: Compared to healthy controls, SPG11 patients exhibited profound changes in body composition, characterized by increased fat tissue index, decreased lean tissue index, and decreased muscle mass. The presence of lymphedema correlated with increased extracellular fluid. The serum levels of the adipokines leptin, resistin, and progranulin were significantly altered in SPG11 while adiponectin and C1q/TNF-related protein 3 (CTRP-3) were unchanged. MRI volumetry revealed a decreased hypothalamic volume in SPG11 patients. Conclusions: Body composition, adipokine levels, and hypothalamic volume are altered in SPG11. Our data indicate a link between obesity and hypothalamic neurodegeneration in SPG11 and imply that specific metabolic interventions may prevent obesity despite severely impaired mobility in SPG11. |
| first_indexed | 2024-03-09T18:05:48Z |
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| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T18:05:48Z |
| publishDate | 2022-11-01 |
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| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-3157e1325b8a466194c679689c0e19ad2023-11-24T09:31:24ZengMDPI AGNutrients2072-66432022-11-011422480310.3390/nu14224803Neurometabolic Dysfunction in SPG11 Hereditary Spastic ParaplegiaMartin Regensburger0Laura Krumm1Manuel Alexander Schmidt2Andreas Schmid3Imke Tabea Spatz4Dominique Cornelius Marterstock5Christoph Kopp6Zacharias Kohl7Arnd Doerfler8Thomas Karrasch9Beate Winner10Jürgen Winkler11Division of Molecular Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDivision of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute of Neuroradiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Internal Medicine III, Gießen University Hospital, 35392 Giessen, GermanyDivision of Molecular Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute of Neuroradiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDivision of Molecular Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute of Neuroradiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Internal Medicine III, Gießen University Hospital, 35392 Giessen, GermanyDivision of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDivision of Molecular Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyBackground: Pathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported in this multisystem neurodegenerative disease. However, a detailed analysis of the metabolic state is lacking. Methods: In order to characterize metabolic alterations, a cross-sectional analysis was performed comparing SPG11 patients (n = 16) and matched healthy controls (n = 16). We quantified anthropometric parameters, body composition as determined by bioimpedance spectroscopy, and serum metabolic biomarkers, and we measured hypothalamic volume by high-field MRI. Results: Compared to healthy controls, SPG11 patients exhibited profound changes in body composition, characterized by increased fat tissue index, decreased lean tissue index, and decreased muscle mass. The presence of lymphedema correlated with increased extracellular fluid. The serum levels of the adipokines leptin, resistin, and progranulin were significantly altered in SPG11 while adiponectin and C1q/TNF-related protein 3 (CTRP-3) were unchanged. MRI volumetry revealed a decreased hypothalamic volume in SPG11 patients. Conclusions: Body composition, adipokine levels, and hypothalamic volume are altered in SPG11. Our data indicate a link between obesity and hypothalamic neurodegeneration in SPG11 and imply that specific metabolic interventions may prevent obesity despite severely impaired mobility in SPG11.https://www.mdpi.com/2072-6643/14/22/4803SPG11obesitybioimpedance spectroscopyleptinadipokineshypothalamus |
| spellingShingle | Martin Regensburger Laura Krumm Manuel Alexander Schmidt Andreas Schmid Imke Tabea Spatz Dominique Cornelius Marterstock Christoph Kopp Zacharias Kohl Arnd Doerfler Thomas Karrasch Beate Winner Jürgen Winkler Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia Nutrients SPG11 obesity bioimpedance spectroscopy leptin adipokines hypothalamus |
| title | Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia |
| title_full | Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia |
| title_fullStr | Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia |
| title_full_unstemmed | Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia |
| title_short | Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia |
| title_sort | neurometabolic dysfunction in spg11 hereditary spastic paraplegia |
| topic | SPG11 obesity bioimpedance spectroscopy leptin adipokines hypothalamus |
| url | https://www.mdpi.com/2072-6643/14/22/4803 |
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