ArticleEndocrinology2016
Blockade of Sphingosine 1-Phosphate Receptor 2 Signaling Attenuates High-Fat Diet-Induced Adipocyte Hypertrophy and Systemic Glucose Intolerance in Mice.
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Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35citing papers in PubMed
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- Sphingosine kinase 2 regulates adipocyte browning and whole-body metabolism.Science advances · 2026Article
- Sex-Dependent S1P-Related Gene Expression in Brown Adipose Tissue Across Exercise and Thermal Conditions.International journal of molecular sciences · 2026Article
- Alternative Receptor Signaling for the Selective and Multifaceted Regulation of Human Brown Adipocytes.International journal of molecular sciences · 2026Review
- Intracellular Sphingosine-1-Phosphate Induces Lipolysis Through Direct Activation of Protein Kinase C Zeta.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- High-concentrate diet decreases lamb fatty acid contents by regulating bile acid composition.Food chemistry: X · 2024Article
- Emerging Roles for Sphingolipids in Cardiometabolic Disease: A Rational Therapeutic Target?Nutrients · 2024Review
- Sphingosine kinase 1 is induced by glucocorticoids in adipose derived stem cells and enhances glucocorticoid mediated signaling in adipose expansion.bioRxiv : the preprint server for biology · 2024Article
- Density of Sphingosine-1-Phosphate Receptors Is Altered in Cortical Nerve-Terminals of Insulin-Resistant Goto-Kakizaki Rats and Diet-Induced Obese Mice.Neurochemical research · 2024Article
- Sphingosine 1-Phosphate Regulates Obesity and Glucose Homeostasis.International journal of molecular sciences · 2024Review
- Chronic Glucocorticoid Exposure Induced an S1PR2-RORγ Axis to Enhance Hepatic Gluconeogenesis in Male Mice.Diabetes · 2023Article
- Fingolimod Modulates the Gene Expression of Proteins Engaged in Inflammation and Amyloid-Beta Metabolism and Improves Exploratory and Anxiety-Like Behavior in Obese Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Opposing Roles of Sphingosine 1-Phosphate Receptors 1 and 2 in Fat Deposition and Glucose Tolerance in Obese Male Mice.Endocrinology · 2023Article
- Article
- Bioactive lipids and metabolic syndrome-a symposium report.Annals of the New York Academy of Sciences · 2022Article
- Integrated Metabolomics and Network Pharmacology Analysis Immunomodulatory Mechanisms of Qifenggubiao Granules.Frontiers in pharmacology · 2022Article
- Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Promoted Osteogenesis by Increasing Vesicle Trafficking, Wnt/CaInternational journal of molecular sciences · 2021Article
- Adipose-Derived Lipid-Binding Proteins: The Good, the Bad and the Metabolic Diseases.International journal of molecular sciences · 2021Review
- Review
- Sphingolipids in metabolic disease: The good, the bad, and the unknown.Cell metabolism · 2021Review
- Inhibition of sphingosine-1-phosphate receptor 2 attenuated ligature-induced periodontitis in mice.Oral diseases · 2021Article
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Authors and funding
16 authors at 5 institutions in 2 countries.
Yoshihiko KitadaDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Kazuo KajitaDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Koichiro TaguchiDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Ichiro MoriDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Masahiro YamauchiDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Takahide IkedaDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Mikako KawashimaDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Motochika AsanoDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Toshiko KajitaDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Tatsuo IshizukaDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Yoshiko BannoDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Itaru KojimaDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Jerold ChunDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Shotaro KamataDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Isao IshiiDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Hiroyuki MoritaDepartment of General Internal Medicine (Y.K., K.K., K.T., I.M., M.Y., T.Ik., M.K., M.A., T.K., H.M.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of General Internal Medicine and Rheumatology (T.Is.), Gifu Municipal Hospital, Gifu 500-8513, Japan; Department of Dermatology (Y.B.), Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Laboratory of Cell Physiology (I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; Molecular and Cellular Neuroscience Department (J.C.), Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; and Department of Biochemistry (S.K., I.I.), Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Gifu University · JPKeio University · JPGifu Municipal Hospital · JPGunma University · JPScripps Research Institute · US
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingosine 1-phosphate (S1P) is known to regulate insulin resistance in hepatocytes, skeletal muscle cells, and pancreatic β-cells. Among its 5 cognate receptors (S1pr1-S1pr5), S1P seems to counteract insulin signaling and confer insulin resistance via S1pr2 in these cells. S1P may also regulate insulin resistance in adipocytes, but the S1pr subtype(s) involved remains unknown. Here, we investigated systemic glucose/insulin tolerance and phenotypes of epididymal adipocytes in high-fat diet (HFD)-fed wild-type and S1pr2-deficient (S1pr2(-/-)) mice. Adult S1pr2(-/-) mice displayed smaller body/epididymal fat tissue weights, but the differences became negligible after 4 weeks with HFD. However, HFD-fed S1pr2(-/-) mice displayed better scores in glucose/insulin tolerance tests and had smaller epididymal adipocytes that expressed higher levels of proliferating cell nuclear antigen than wild-type mice. Next, proliferation/differentiation of 3T3-L1 and 3T3-F442A preadipocytes were examined in the presence of various S1pr antagonists: JTE-013 (S1pr2 antagonist), VPC-23019 (S1pr1/S1pr3 antagonist), and CYM-50358 (S1pr4 antagonist). S1P or JTE-013 treatment of 3T3-L1 preadipocytes potently activated their proliferation and Erk phosphorylation, whereas VPC-23019 inhibited both of these processes, and CYM-50358 had no effects. In contrast, S1P or JTE-013 treatment inhibited adipogenic differentiation of 3T3-F442A preadipocytes, whereas VPC-23019 activated it. The small interfering RNA knockdown of S1pr2 promoted proliferation and inhibited differentiation of 3T3-F442A preadipocytes, whereas that of S1pr1 acted oppositely. Moreover, oral JTE-013 administration improved glucose tolerance/insulin sensitivity in ob/ob mice. Taken together, S1pr2 blockade induced proliferation but suppressed differentiation of (pre)adipocytes both in vivo and in vitro, highlighting a novel therapeutic approach for obesity/type 2 diabetes.
Indexed as
Diet, High-Fat3T3-L1 CellsAdipocytesAdipogenesisAnimalsBody WeightCell DifferentiationCell EnlargementCell ProliferationFemaleGlucose IntoleranceMaleMiceMice, KnockoutPhosphoserinePyrazolesJTE 013PhosphoserinePyrazolesPyridinesReceptors, Lysosphingolipidsphingosine-1-phosphate receptor-2, mouseSphingosine-1-Phosphate ReceptorsVPC23019
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