Liver X receptor alpha (LXRα) plays important roles in lipid metabolism and inflammation. Therefore, it is essential for protection against atherosclerosis (AS). In AS plaques, the key cells involved in lipid metabolism and inflammation are macrophages. However, the mechanism by which LXRα regulates macrophage involvement in AS formation remains unclear. In this study, we first confirmed the effects of an LXRα agonist (T0901317) and antagonist (GSK2033) on foam cell formation and inflammation and . Indeed, T0901317 reduced the number of macrophages in AS plaques and decreased the number of migrated macrophages, as assessed using an transwell assay. Next, we investigated the relationship between the reduction in macrophages in AS plaques and cytokine levels or foam cell formation. The results show that T0901317 reduced the number of high cholesterol-induced M1 macrophages by converting them into M2 macrophages and . Due to this phenotypic transition of macrophages, the inflammatory response was alleviated, and lipid metabolism was enhanced in AS plaques. This effect was achieved by promoting the expression of reverse transporters (ATP-binding cassette transporter member 1 and ATP-binding cassette subfamily G member 1) and inhibiting the phosphorylation of nuclear factor-κB-mediated phosphorylation.
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Genet Epidemiol
January 2025
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C).
View Article and Find Full Text PDFFront Microbiol
December 2024
Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia.
Introduction: Lactic acid bacteria are prized for their probiotic benefits and gut health improvements. This study assessed five LAB isolates from Neera, with RAMULAB51 (, GenBank ON171686.1) standing out for its high hydrophobicity, auto-aggregation, antimicrobial activity, and enzyme inhibition.
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Objectives: Define how the regulatory factor Nipsnap1 integrates with lipid metabolism.
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View Article and Find Full Text PDFExposure to saturated fatty acids (SFAs), such as palmitic acid, can lead to cellular metabolic dysfunction known as lipotoxicity. Although canonical adaptive metabolic processes like lipid storage or desaturation are known cellular responses to saturated fat exposure, the link between SFA metabolism and organellar biology remains an area of active inquiry. We performed a genome-wide CRISPR knockout screen in human epithelial cells to identify modulators of SFA toxicity.
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