Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolism
Conditions related to cardiometabolic disease, including metabolic syndrome and type 2 diabetes, are common among men with Klinefelter syndrome (KS). The molecular mechanisms underlying this aberrant metabolism in KS are largely unknown, although there is an assumption that chronic testosterone defi...
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| Format: | Article |
| Language: | English |
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Bioscientifica
2023-04-01
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| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | https://ec.bioscientifica.com/view/journals/ec/12/5/EC-22-0523.xml |
| _version_ | 1827963967017844736 |
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| author | Shanlee M Davis Rhianna Urban Angelo D’Alessandro Julie A Reisz Christine L Chan Megan Kelsey Susan Howell Nicole Tartaglia Philip Zeitler Peter Baker II |
| author_facet | Shanlee M Davis Rhianna Urban Angelo D’Alessandro Julie A Reisz Christine L Chan Megan Kelsey Susan Howell Nicole Tartaglia Philip Zeitler Peter Baker II |
| author_sort | Shanlee M Davis |
| collection | DOAJ |
| description | Conditions related to cardiometabolic disease, including metabolic syndrome and type 2 diabetes, are common among men with Klinefelter syndrome (KS). The molecular mechanisms underlying this aberrant metabolism in KS are largely unknown, although there is an assumption that chronic testosterone deficiency play s a role. This cross-sectional study compared plasma metabolites in 31 pubertal adolescent males with KS to 32 controls of similar age (14 ± 2 years), pubertal stage, and body mass index z-score of 0.1 ± 1.2 and then between testosterone-treated (n = 16) and untreated males with KS. The plasma metabolome in males with KS was distinctly different from that in controls, with 22% of measured metabolites having a differential abundance and seven metabolites nearly completely separating KS from controls (area under the curve > 0.9, P < 0.0001). Multiple saturated free fatty acids were higher in KS, while mono- and polyunsaturated fatty acids were lower, and the top significantl y enriched pathway was mitochondrial β-oxidation of long-chain saturated fatty acids (enrichment rati o 16, P < 0.0001). In contrast, there were no observed differences in meta bolite concentrations between testosterone-treated and untreated individuals with KS. In conclusion, the plasma metabolome profile in adolescent males with KS is distinctly diff erent from that in males without KS independent of age, obesity, pubertal development, or testosterone treatment status and is suggestive of differences in mitochondrial β-oxidation. |
| first_indexed | 2024-04-09T17:07:42Z |
| format | Article |
| id | doaj.art-7715c9af0b594652bec767cf26bc0cfb |
| institution | Directory Open Access Journal |
| issn | 2049-3614 |
| language | English |
| last_indexed | 2024-04-09T17:07:42Z |
| publishDate | 2023-04-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-7715c9af0b594652bec767cf26bc0cfb2023-04-20T10:54:54ZengBioscientificaEndocrine Connections2049-36142023-04-0112519https://doi.org/10.1530/EC-22-0523Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolismShanlee M Davis0Rhianna Urban1Angelo D’Alessandro2Julie A Reisz3Christine L Chan4Megan Kelsey5Susan Howell6Nicole Tartaglia7Philip Zeitler8Peter Baker II9Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA; eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USADepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USADepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USADepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USADepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USADepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA; eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA; eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA; eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USAConditions related to cardiometabolic disease, including metabolic syndrome and type 2 diabetes, are common among men with Klinefelter syndrome (KS). The molecular mechanisms underlying this aberrant metabolism in KS are largely unknown, although there is an assumption that chronic testosterone deficiency play s a role. This cross-sectional study compared plasma metabolites in 31 pubertal adolescent males with KS to 32 controls of similar age (14 ± 2 years), pubertal stage, and body mass index z-score of 0.1 ± 1.2 and then between testosterone-treated (n = 16) and untreated males with KS. The plasma metabolome in males with KS was distinctly different from that in controls, with 22% of measured metabolites having a differential abundance and seven metabolites nearly completely separating KS from controls (area under the curve > 0.9, P < 0.0001). Multiple saturated free fatty acids were higher in KS, while mono- and polyunsaturated fatty acids were lower, and the top significantl y enriched pathway was mitochondrial β-oxidation of long-chain saturated fatty acids (enrichment rati o 16, P < 0.0001). In contrast, there were no observed differences in meta bolite concentrations between testosterone-treated and untreated individuals with KS. In conclusion, the plasma metabolome profile in adolescent males with KS is distinctly diff erent from that in males without KS independent of age, obesity, pubertal development, or testosterone treatment status and is suggestive of differences in mitochondrial β-oxidation.https://ec.bioscientifica.com/view/journals/ec/12/5/EC-22-0523.xmlmetabolomicsklinefelter syndromesex chromosome aneuploidyfatty acid metabolismmitochondrial function |
| spellingShingle | Shanlee M Davis Rhianna Urban Angelo D’Alessandro Julie A Reisz Christine L Chan Megan Kelsey Susan Howell Nicole Tartaglia Philip Zeitler Peter Baker II Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolism Endocrine Connections metabolomics klinefelter syndrome sex chromosome aneuploidy fatty acid metabolism mitochondrial function |
| title | Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolism |
| title_full | Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolism |
| title_fullStr | Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolism |
| title_full_unstemmed | Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolism |
| title_short | Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolism |
| title_sort | unique plasma metabolite signature for adolescents with klinefelter syndrome reveals altered fatty acid metabolism |
| topic | metabolomics klinefelter syndrome sex chromosome aneuploidy fatty acid metabolism mitochondrial function |
| url | https://ec.bioscientifica.com/view/journals/ec/12/5/EC-22-0523.xml |
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