ArticleHepatology (Baltimore, Md.)2015
Conjugated bile acid-activated S1P receptor 2 is a key regulator of sphingosine kinase 2 and hepatic gene expression.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Who cites it
135 citing papers in PubMed, 203 citations in OpenAlex.
- Bile salt hydrolase activity as a rational target for MASLD therapy.Gut microbes · 2026Article
- The gut microbiome-bile acid-FXR interplay: a pivotal axis in metabolic and gastrointestinal diseases.Gut microbes · 2026Review
- LncRNA H19 as a key regulator in biliary atresia: insights into pathogenesis and potential therapeutic targets.Annals of medicine · 2026Review
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- Sphingosine kinase 2 regulates adipocyte browning and whole-body metabolism.Science advances · 2026Article
- Plasma metabolites, dietary intakes, and breast cancer incidence: a prospective case-cohort study in NutriNet-Santé.The American journal of clinical nutrition · 2026Article
- Decoding the S1P-S1PR axis in cancer: Mechanisms, pathways and therapeutic horizons (Review).Biomedical reports · 2026Review
- Gut microbiome and bile acid metabolism in liver disease: Mechanisms, clinical implications, and therapeutic opportunities.Pharmacological reviews · 2026Review
- Cholestasis in Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- Fetal programming by the parental microbiome of offspring behavior, and DNA methylation and gene expression within the hippocampus.Microbiome · 2025Article
- Gut microbiota in regulatory T cell generation and function: mechanisms and health implications.Gut microbes · 2025Review
- Microbial bile acid modifications: current understandings, key problems, and future perspectives.Science China. Life sciences · 2025Review
- Review
- Biological functions and pharmacological behaviors of bile acids in metabolic diseases.Journal of advanced research · 2025Review
- Genomics-informed drug-repurposing strategy identifies two therapeutic targets for preventing liver disease associated with metabolic dysfunction.American journal of human genetics · 2025Article
- The gut microbiota-bile acid axis: a crucial regulator of immune function and metabolic health.World journal of microbiology & biotechnology · 2025Review
- Conjugated bile acids promote metabolic dysfunction-associated steatotic liver disease through inducing nuclear translocation of sphingosine-1-phosphate receptor 2 to disrupt peroxisome proliferator-activated receptor alpha.Cell communication and signaling : CCS · 2025Article
- Review of roles of RNA-binding proteins on NAFLD and the related pharmaceutical measures.Biomolecules & biomedicine · 2025Review
- Targeting Bile-Acid Metabolism: Nutritional and Microbial Approaches to Alleviate Ulcerative Colitis.Nutrients · 2025Review
- Transcriptomics, lipidomics, and single-nucleus RNA sequencing integration: exploring sphingolipids in MASH-HCC progression.Cell & bioscience · 2025Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 1 institution in 2 countries.
Funding
Abstract
unlabelledBile acids are important hormones during the feed/fast cycle, allowing the liver to coordinately regulate nutrient metabolism. How they accomplish this has not been fully elucidated. Conjugated bile acids activate both the ERK1/2 and AKT signaling pathways via sphingosine 1-phosphate receptor 2 (S1PR2) in rodent hepatocytes and in vivo. Here, we report that feeding mice a high-fat diet, infusion of taurocholate into the chronic bile fistula rat, or overexpression of the gene encoding S1PR2 in mouse hepatocytes significantly upregulated hepatic sphingosine kinase 2 (SphK2) but not SphK1. Key genes encoding nuclear receptors/enzymes involved in nutrient metabolism were significantly downregulated in livers of S1PR2(-/-) and SphK2(-/-) mice. In contrast, overexpression of the gene encoding S1PR2 in primary mouse hepatocytes differentially increased SphK2, but not SphK1, and mRNA levels of key genes involved in nutrient metabolism. Nuclear levels of sphingosine-1-phosphate, an endogenous inhibitor of histone deacetylases 1 and 2, as well as the acetylation of histones H3K9, H4K5, and H2BK12 were significantly decreased in hepatocytes prepared from S1PR2(-/-) and SphK2(-/-) mice.
conclusionBoth S1PR2(-/-) and SphK2(-/-) mice rapidly developed fatty livers on a high-fat diet, suggesting the importance of conjugated bile acids, S1PR2, and SphK2 in regulating hepatic lipid metabolism.
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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.