Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism.

Autor:	Escarcega RD; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Vijay Kumar MJ; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Kyriakopoulos VE; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Ortiz GJ; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Gusdon AM; Department of Neurosurgery, the University of Texas McGovern Medical School at Houston, TX, USA., Fan H; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Peesh P; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Conesa MPB; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Colpo GD; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Ahnstedt HW; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Couture L; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Kim SH; Department 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., Hinojosa M; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Farrell CM; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Marrelli SP; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Urayama A; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Ganesh BP; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., Schulz PE; Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA., McCullough LD; Department 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., Tsvetkov AS; Department 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.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Nov 13. Date of Electronic Publication: 2024 Nov 13.
DOI:	10.1101/2024.11.11.623108
Abstrakt:	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. Competing Interests: Competing interests Paul E. Schulz is a consultant and speaker for Eli Lilly, Eisai, and Acadia Pharmaceuticals.
Databáze:	MEDLINE
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