Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism
Alzheimer's disease (AD) affects more women than men. Although women live longer than men, it is not longevity alone, but other factors, including metabolic changes, that contribute to the higher risk of AD in women. Metabolic pathways have been implicated in AD progression, but studies to date...
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Elsevier
2025-01-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996124003498 |
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| author | Rocio Diaz Escarcega Vijay Kumar M. J. Vasilia E. Kyriakopoulos Guadalupe J. Ortiz Aaron M. Gusdon Huihui Fan Pedram Peesh Maria P. Blasco Conesa Gabriela Delevati Colpo Hilda W. Ahnstedt Lucy Couture Stella H. Kim Miriam Hinojosa Christine M. Farrell Sean P. Marrelli Akihiko Urayama Bhanu P. Ganesh Paul E. Schulz Louise D. McCullough Andrey S. Tsvetkov |
| author_facet | Rocio Diaz Escarcega Vijay Kumar M. J. Vasilia E. Kyriakopoulos Guadalupe J. Ortiz Aaron M. Gusdon Huihui Fan Pedram Peesh Maria P. Blasco Conesa Gabriela Delevati Colpo Hilda W. Ahnstedt Lucy Couture Stella H. Kim Miriam Hinojosa Christine M. Farrell Sean P. Marrelli Akihiko Urayama Bhanu P. Ganesh Paul E. Schulz Louise D. McCullough Andrey S. Tsvetkov |
| author_sort | Rocio Diaz Escarcega |
| collection | DOAJ |
| description | Alzheimer's disease (AD) affects more women than men. Although women live longer than men, it is not longevity alone, but other factors, including metabolic changes, that contribute to the higher risk of AD in women. Metabolic pathways have been implicated in AD progression, but studies to date examined targeted pathways, leaving many metabolites unmeasured. Sex is often a neglected biological variable, and most metabolomic studies were not designed to investigate sex differences in metabolomic profiles. Here, we performed untargeted metabolomic profiling of sera from male and female patients with mild cognitive impairment (MCI), a common precursor to AD, and matched controls. We discovered significant metabolic changes in individuals with MCI, and found several pathways that were strongly associated with sex. Peptide energy metabolism demonstrated sexual dimorphism. Lipid pathways exhibited the strongest differences between female and male MCI patients, including specific phosphatidylcholine lipids, lysophospholipids, long-chain fatty acids, and monoacylglycerols. 1-palmitoleoyl glycerol and 1-arachidonoyl glycerol were higher in female MCI subjects than in male MCI subjects with no differences between control males and females. Conversely, specific dicarboxylic fatty acids were lower in female MCI subjects than male MCI subjects. In cultured astrocytes, 1-arachidonoyl glycerol promoted phosphorylation of the transcriptional regulator sphingosine kinase 2, which was inhibited by the transient receptor potential vanilloid 1 receptor antagonists, as well as chromatin remodelling. Overall, we identified novel sex-specific metabolites in MCI patients that could serve as biomarkers of MCI in both sexes, help further define AD etiology, and reveal new potential prevention strategies for AD. |
| format | Article |
| id | doaj-art-169323e61f4244ec9171e8061bea4513 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-169323e61f4244ec9171e8061bea45132025-01-07T04:17:05ZengElsevierNeurobiology of Disease1095-953X2025-01-01204106747Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolismRocio Diaz Escarcega0Vijay Kumar M. J.1Vasilia E. Kyriakopoulos2Guadalupe J. Ortiz3Aaron M. Gusdon4Huihui Fan5Pedram Peesh6Maria P. Blasco Conesa7Gabriela Delevati Colpo8Hilda W. Ahnstedt9Lucy Couture10Stella H. Kim11Miriam Hinojosa12Christine M. Farrell13Sean P. Marrelli14Akihiko Urayama15Bhanu P. Ganesh16Paul E. Schulz17Louise D. McCullough18Andrey S. Tsvetkov19Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurosurgery, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA; The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA; The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USADepartment of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA; The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA; UTHealth Consortium on Aging, the University of Texas McGovern Medical School, Houston, TX, USA; Corresponding author at: Department of Neurology, University of Texas, Houston Medical School, Houston, TX 77030, USA.Alzheimer's disease (AD) affects more women than men. Although women live longer than men, it is not longevity alone, but other factors, including metabolic changes, that contribute to the higher risk of AD in women. Metabolic pathways have been implicated in AD progression, but studies to date examined targeted pathways, leaving many metabolites unmeasured. Sex is often a neglected biological variable, and most metabolomic studies were not designed to investigate sex differences in metabolomic profiles. Here, we performed untargeted metabolomic profiling of sera from male and female patients with mild cognitive impairment (MCI), a common precursor to AD, and matched controls. We discovered significant metabolic changes in individuals with MCI, and found several pathways that were strongly associated with sex. Peptide energy metabolism demonstrated sexual dimorphism. Lipid pathways exhibited the strongest differences between female and male MCI patients, including specific phosphatidylcholine lipids, lysophospholipids, long-chain fatty acids, and monoacylglycerols. 1-palmitoleoyl glycerol and 1-arachidonoyl glycerol were higher in female MCI subjects than in male MCI subjects with no differences between control males and females. Conversely, specific dicarboxylic fatty acids were lower in female MCI subjects than male MCI subjects. In cultured astrocytes, 1-arachidonoyl glycerol promoted phosphorylation of the transcriptional regulator sphingosine kinase 2, which was inhibited by the transient receptor potential vanilloid 1 receptor antagonists, as well as chromatin remodelling. Overall, we identified novel sex-specific metabolites in MCI patients that could serve as biomarkers of MCI in both sexes, help further define AD etiology, and reveal new potential prevention strategies for AD.http://www.sciencedirect.com/science/article/pii/S0969996124003498Sex differencesCognitionMetabolomicsLipids1-MonoacylglycerolSphingosine kinase 2 |
| spellingShingle | Rocio Diaz Escarcega Vijay Kumar M. J. Vasilia E. Kyriakopoulos Guadalupe J. Ortiz Aaron M. Gusdon Huihui Fan Pedram Peesh Maria P. Blasco Conesa Gabriela Delevati Colpo Hilda W. Ahnstedt Lucy Couture Stella H. Kim Miriam Hinojosa Christine M. Farrell Sean P. Marrelli Akihiko Urayama Bhanu P. Ganesh Paul E. Schulz Louise D. McCullough Andrey S. Tsvetkov Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism Neurobiology of Disease Sex differences Cognition Metabolomics Lipids 1-Monoacylglycerol Sphingosine kinase 2 |
| title | Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism |
| title_full | Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism |
| title_fullStr | Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism |
| title_full_unstemmed | Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism |
| title_short | Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism |
| title_sort | serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism |
| topic | Sex differences Cognition Metabolomics Lipids 1-Monoacylglycerol Sphingosine kinase 2 |
| url | http://www.sciencedirect.com/science/article/pii/S0969996124003498 |
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