Type 2 diabetes mellitus (T2DM) has become a tremendous problem in public health nowadays. High-density lipoprotein (HDL) refers to a group of heterogeneous particles that circulate in blood, and a recent research finds that HDL acts a pivotal part of glucose metabolism. To understand systemic metabolic changes correlated with HDL in glucose metabolism, we applied LC-MS-based metabolomics and lipidomics to detect metabolomic and lipidomic profiles of plasma from apoA-I knockout mice fed a high-fat diet. Multivariate analysis was applied to differentiate apoA-I knockout mice and controls, and potential biomarkers were found. Pathway analysis demonstrated that several metabolic pathways such as aminoacyl-tRNA biosynthesis, arginine and proline metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis were dysregulated in apoA-I knockout mice. This study may provide a new insight into the underlying pathogenesis in T2DM and prove that LC-MS-based metabolomics and lipidomics are powerful approaches in finding potential biomarkers and disturbed pathways.
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http://dx.doi.org/10.1021/acs.jproteome.8b00290 | DOI Listing |
Metabolism
February 2025
Tianjin Key Laboratory of Metabolic Diseases, Department of Physiology and Pathophysiology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China; Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China. Electronic address:
Background And Aims: Atherosclerotic cardiovascular diseases are the leading cause of death. Apolipoprotein A-I (apoA-I) mediates cholesterol efflux to lower the risks of atherosclerosis. Elevating circulating apoA-I is an effective strategy for atheroprotection.
View Article and Find Full Text PDFJ Biol Chem
November 2024
Department of Cell Biology, SUNY Downstate Health Sciences University, Brooklyn, New York, USA; Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System, Brooklyn, New York, USA. Electronic address:
J Neuroinflammation
September 2024
Department of Medicine, University of California, San Diego, La Jolla, San Diego, CA, 92093, USA.
Microglia-driven neuroinflammation plays an important role in the development of Alzheimer's disease. Microglia activation is accompanied by the formation and chronic expression of TLR4 inflammarafts, defined as enlarged and cholesterol-rich lipid rafts serving as an assembly platform for TLR4 dimers and complexes of other inflammatory receptors. The secreted apoA-I binding protein (APOA1BP or AIBP) binds TLR4 and selectively targets cholesterol depletion machinery to TLR4 inflammaraft-expressing inflammatory, but not homeostatic microglia.
View Article and Find Full Text PDFMethods Mol Biol
July 2024
Bascom Palmer Eye Institute, Miami Integrative Metabolomics Research Center, University of Miami, Miami, FL, USA.
The role of lipid metabolic pathways in the pathophysiology of primary open-angle glaucoma (POAG) has been thoroughly elucidated, with pathways involved in lipid-related disorders such as hypercholesterolemia and hyperlipoprotein accumulation being of particular interest. The ABCA1/apoA-1 transduction pathway moderates reverse cholesterol transport (RCT), facilitating the transport of free cholesterol (FC) and phospholipids (PL) and preventing intracellular lipid aggregates in retinal ganglion cells (RGCs) due to excess FCs and PLs. A deficiency of ABCA1 transporters, and thus, dysregulation of the ABCA1/apoA-1 transduction pathway, may potentiate cellular lipid accumulation, which affects the structural and mechanical features of the cholesterol-rich RGC membranes.
View Article and Find Full Text PDFJ Immunol
August 2024
Laboratory of Asthma and Lung Inflammation, Critical Care Medicine and Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Neutrophils play important roles in inflammatory airway diseases. In this study, we assessed whether apolipoprotein A-I modifies neutrophil heterogeneity as part of the mechanism by which it attenuates acute airway inflammation. Neutrophilic airway inflammation was induced by daily intranasal administration of LPS plus house dust mite (LPS+HDM) to Apoa1-/- and Apoa1+/+ mice for 3 d.
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