دورية أكاديمية
An E115A Missense Variant in CERS2 Is Associated With Increased Sleeping Energy Expenditure and Hepatic Insulin Resistance in American Indians.
| العنوان: | An E115A Missense Variant in CERS2 Is Associated With Increased Sleeping Energy Expenditure and Hepatic Insulin Resistance in American Indians. |
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| المؤلفون: | Heinitz S; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.; Department of Internal Medicine, Clinic for Endocrinology, Nephrology and Rheumatology, University of Leipzig, Leipzig, Germany.; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig, Philipp-Rosenthal-Strasse 27, Leipzig, Germany., Traurig M; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ., Krakoff J; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ., Rabe P; Faculty of Medicine, Rudolf Schönheimer Institute of Biochemistry, Leipzig University, Leipzig, Germany., Stäubert C; Faculty of Medicine, Rudolf Schönheimer Institute of Biochemistry, Leipzig University, Leipzig, Germany., Kobes S; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ., Hanson RL; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ., Stumvoll M; Department of Internal Medicine, Clinic for Endocrinology, Nephrology and Rheumatology, University of Leipzig, Leipzig, Germany.; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig, Philipp-Rosenthal-Strasse 27, Leipzig, Germany., Blüher M; Department of Internal Medicine, Clinic for Endocrinology, Nephrology and Rheumatology, University of Leipzig, Leipzig, Germany.; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig, Philipp-Rosenthal-Strasse 27, Leipzig, Germany., Bogardus C; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ., Baier L; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ., Piaggi P; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.; Department of Information Engineering, University of Pisa, Pisa, Italy. |
| المصدر: | Diabetes [Diabetes] 2024 Aug 01; Vol. 73 (8), pp. 1361-1371. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Alexandria, VA : American Diabetes Association Original Publication: [New York, American Diabetes Association] |
| مواضيع طبية MeSH: | Energy Metabolism*/genetics , Indians, North American*/genetics , Insulin Resistance*/genetics , Liver*/metabolism , Membrane Proteins*/genetics , Membrane Proteins*/metabolism , Sphingosine N-Acyltransferase*/genetics , Sphingosine N-Acyltransferase*/metabolism, Adult ; Female ; Humans ; Male ; Middle Aged ; Glucose Clamp Technique ; Hep G2 Cells ; Mutation, Missense ; Sleep/genetics ; Sleep/physiology ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism |
| مستخلص: | Genetic determinants of interindividual differences in energy expenditure (EE) are largely unknown. Sphingolipids, such as ceramides, have been implicated in the regulation of human EE via mitochondrial uncoupling. In this study, we investigated whether genetic variants within enzymes involved in sphingolipid synthesis and degradation affect EE and insulin-related traits in a cohort of American Indians informative for 24-h EE and glucose disposal rates during a hyperinsulinemic-euglycemic clamp. Association analysis of 10,084 genetic variants within 28 genes involved in sphingolipid pathways identified a missense variant (rs267738, A>C, E115A) in exon 4 of CERS2 that was associated with higher sleeping EE (116 kcal/day) and increased rates of endogenous glucose production during basal (5%) and insulin-stimulated (43%) conditions, both indicators of hepatic insulin resistance. The rs267738 variant did not affect ceramide synthesis in HepG2 cells but resulted in a 30% decrease in basal mitochondrial respiration. In conclusion, we provide evidence that the CERS2 rs267738 missense variant may influence hepatic glucose production and postabsorptive sleeping metabolic rate. (© 2024 by the American Diabetes Association.) |
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| معلومات مُعتمدة: | Z01 DK069015 United States ImNIH Intramural NIH HHS; DK069015-36 United States DK NIDDK NIH HHS |
| المشرفين على المادة: | EC 2.3.1.24 (CERS2 protein, human) 0 (Membrane Proteins) EC 2.3.1.24 (Sphingosine N-Acyltransferase) 0 (Tumor Suppressor Proteins) |
| تواريخ الأحداث: | Date Created: 20240522 Date Completed: 20240719 Latest Revision: 20240814 |
| رمز التحديث: | 20240814 |
| مُعرف محوري في PubMed: | PMC11262042 |
| DOI: | 10.2337/db23-0690 |
| PMID: | 38776413 |
| قاعدة البيانات: | MEDLINE |
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