ArticleThe Journal of biological chemistry2014
Hepatic apolipoprotein M (apoM) overexpression stimulates formation of larger apoM/sphingosine 1-phosphate-enriched plasma high density lipoprotein.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 79 citations in OpenAlex.
- Trial
- Effects of Replacing Dietary Monounsaturated Fat With Carbohydrate on HDL (High-Density Lipoprotein) Protein Metabolism and Proteome Composition in Humans.Arteriosclerosis, thrombosis, and vascular biology · 2019Trial
- Plasma apoM and S1P levels are inversely associated with mortality in African Americans with type 2 diabetes mellitus.Journal of lipid research · 2019Trial
- APOM-associated inflammation and apoptosis in stroke-exacerbated myocardial infarction: implications for brain-heart interactions.Apoptosis : an international journal on programmed cell death · 2026Article
- Molecular characteristics of apolipoprotein M and its biological functions in kidney diseases.Molecular and cellular biochemistry · 2026Review
- Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytes.Nature communications · 2026Article
- Mechanisms of high-density lipoprotein in regulating blood-brain barrier function: insights and implications.Fluids and barriers of the CNS · 2025Review
- Apolipoprotein M attenuates age-related macular degeneration phenotypes via sphingosine-1-phosphate signaling and lysosomal lipid catabolism.Nature communications · 2025Article
- Sodium-Glucose Cotransporter Inhibition Preserves Apolipoprotein M During Acute Inflammation in Mice and Humans.JACC. Advances · 2025Article
- Apolipoprotein A1 (CSL112) Increases Lecithin-Cholesterol Acyltransferase Levels in HDL Particles and Promotes Reverse Cholesterol Transport.JACC. Basic to translational science · 2025Article
- ApoM maintains cellular homeostasis between mitophagy and apoptosis by affecting the stability of Nnt mRNA through the Zic3-ApoM-Elavl2-Nnt axis during neural tube closure.Cell death & disease · 2025Article
- Alterations of lipoprotein subfractions in GH-deficient adults.Frontiers in endocrinology · 2025Article
- Article
- Kidney derived apolipoprotein M and its role in acute kidney injury.Frontiers in pharmacology · 2024Article
- Apolipoprotein M Attenuates Anthracycline Cardiotoxicity and Lysosomal Injury.JACC. Basic to translational science · 2023Article
- The FoxOs are in the ApoM house.The Journal of clinical investigation · 2022Article
- Sphingosine 1-Phosphate Metabolism and Signaling.Advances in experimental medicine and biology · 2022Article
- Molecular Mechanisms of Sphingolipid Transport on Plasma Lipoproteins.Advances in experimental medicine and biology · 2022Article
- Apolipoprotein M and Sphingosine-1-Phosphate Receptor 1 Promote the Transendothelial Transport of High-Density Lipoprotein.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Glycation of HDL Polymerizes Apolipoprotein M and Attenuates Its Capacity to Bind to Sphingosine 1-Phosphate.Journal of atherosclerosis and thrombosis · 2021Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Apolipoprotein M (apoM), a lipocalin family member, preferentially associates with plasma HDL and binds plasma sphingosine 1-phosphate (S1P), a signaling molecule active in immune homeostasis and endothelial barrier function. ApoM overexpression in ABCA1-expressing HEK293 cells stimulated larger nascent HDL formation, compared with cells that did not express apoM; however, the in vivo role of apoM in HDL metabolism remains poorly understood. To test whether hepatic apoM overexpression increases plasma HDL size, we generated hepatocyte-specific apoM transgenic (APOM Tg) mice, which had an ∼3-5-fold increase in plasma apoM levels compared with wild-type mice. Although HDL cholesterol concentrations were similar to wild-type mice, APOM Tg mice had larger plasma HDLs enriched in apoM, cholesteryl ester, lecithin:cholesterol acyltransferase, and S1P. Despite the presence of larger plasma HDLs in APOM Tg mice, in vivo macrophage reverse cholesterol transport capacity was similar to that in wild-type mice. APOM Tg mice had an ∼5-fold increase in plasma S1P, which was predominantly associated with larger plasma HDLs. Primary hepatocytes from APOM Tg mice generated larger nascent HDLs and displayed increased sphingolipid synthesis and S1P secretion. Inhibition of ceramide synthases in hepatocytes increased cellular S1P levels but not S1P secretion, suggesting that apoM is rate-limiting in the export of hepatocyte S1P. Our data indicate that hepatocyte-specific apoM overexpression generates larger nascent HDLs and larger plasma HDLs, which preferentially bind apoM and S1P, and stimulates S1P biosynthesis for secretion. The unique apoM/S1P-enriched plasma HDL may serve to deliver S1P to extrahepatic tissues for atheroprotection and may have other as yet unidentified functions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.