Cortical lipid metabolic pathway alteration of early Alzheimer's disease and candidate drugs screen.

BACKGROUND: Lipid metabolism changes occur in early Alzheimer's disease (AD) patients. Yet little is known about metabolic gene changes in early AD cortex. METHODS: The lipid metabolic genes selected from two datasets (GSE39420 and GSE118553) were analyzed with enrichment analysis. Protein-protein interaction network construction and correlation analyses were used to screen core genes. Literature analysis and molecular docking were applied to explore potential therapeutic drugs. RESULTS: 60 lipid metabolic genes differentially expressed in early AD patients' cortex were screened. Bioinformatics analyses revealed that up-regulated genes were mainly focused on mitochondrial fatty acid oxidation and mediating the activation of long-chain fatty acids, phosphoproteins, and cholesterol metabolism. Down-regulated genes were mainly focused on lipid transport, carboxylic acid metabolic process, and neuron apoptotic process. Literature reviews and molecular docking results indicated that ACSL1, ACSBG2, ACAA2, FABP3, ALDH5A1, and FFAR4 were core targets for lipid metabolism disorder and had a high binding affinity with compounds including adenosine phosphate, oxidized Photinus luciferin, BMS-488043, and candidate therapeutic drugs especially bisphenol A, benzo(a)pyrene, ethinyl estradiol. CONCLUSIONS: AD cortical lipid metabolism disorder was associated with the dysregulation of the PPAR signaling pathway, glycerophospholipid metabolism, adipocytokine signaling pathway, fatty acid biosynthesis, fatty acid degradation, ferroptosis, biosynthesis of unsaturated fatty acids, and fatty acid elongation. Candidate drugs including bisphenol A, benzo(a)pyrene, ethinyl estradiol, and active compounds including adenosine phosphate, oxidized Photinus luciferin, and BMS-488043 have potential therapeutic effects on cortical lipid metabolism disorder of early AD.

Application of plasma lipidomics in studying the response of patients with essential hypertension to antihypertensive drug therapy.

Hypertension is a key risk factor in the progression of cardiovascular disease (CVD). Dyslipidemia, a strong predictor of CVD, frequently coexists with hypertension. Therefore, the control of hypertension and dyslipidemia may help reduce CVD morbidity and mortality. In the present study, the therapeutic effects of antihypertensive agents on blood pressure control and plasma lipid metabolism were evaluated. The plasma lipid profiles of patients with treated (n = 25) or untreated (n = 30) essential hypertension as well as of subjects with normotension (n = 28) were analyzed using liquid chromatography mass spectrometry. Principal component analysis of the lipidomics data revealed distinct clusters among studied subjects across three human populations. Phosphatidylcholines and triacylglycerols (TG) dominated the pattern of hypertension-influenced plasma lipid metabolism. Discriminatory lipid metabolites were analyzed using one-way analysis of variance followed by a post hoc multiple comparison correction. TG lipid class was significantly increased by 49.0% (p < 0.001) in hypertensive vs. normotensive groups while tended to decrease (-21.2%, p = 0.054) in hypertensive patients after treatment. Total cholesteryl esters were significantly decreased by -16.9% (p < 0.001) in hypertensive patients after treatment. In particular, a large number of individual neutral lipid species were significantly elevated in hypertensive subjects but significantly decreased after treatment with antihypertensive agents. The present study applied, for the first time, a systems biology based lipidomics approach to investigate differentiation among plasma lipid metabolism of patients with treated/untreated essential hypertension and subjects with normotension. Our results demonstrate that antihypertensive medications to lower blood pressure of hypertensive patients to target levels produced moderate plasma lipid metabolism improvement of patients with hypertension.