دورية أكاديمية
أعرض في EDS

Global deletion of NTPDase3 protects against diet-induced obesity by increasing basal energy metabolism.

التفاصيل البيبلوغرافية
العنوان: Global deletion of NTPDase3 protects against diet-induced obesity by increasing basal energy metabolism.
المؤلفون: Sandhu B; Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Perez-Matos MC; Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Tran S; Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Singhal G; Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Syed I; Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Feldbrügge L; Department of Surgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Mitsuhashi S; Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Pelletier J; Centre de recherche du CHU de Québec - Université Laval, Québec City, QC G1V 4G2, Canada., Huang J; Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Yalcin Y; Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Csizmadia E; Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Tiwari-Heckler S; Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Enjyoji K; Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Sévigny J; Centre de recherche du CHU de Québec - Université Laval, Québec City, QC G1V 4G2, Canada; Département de microbiologie-infectiologie et d'immunologie, Faculté de Médecine, Université Laval, Québec City, QC G1V 0A6, Canada., Maratos-Flier E; Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Robson SC; Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Anesthesiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: srobson@bidmc.harvard.edu., Jiang ZG; Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: zgjiang@bidmc.harvard.edu.
المصدر: Metabolism: clinical and experimental [Metabolism] 2021 May; Vol. 118, pp. 154731. Date of Electronic Publication: 2021 Feb 23.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Elsevier Inc Country of Publication: United States NLM ID: 0375267 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-8600 (Electronic) Linking ISSN: 00260495 NLM ISO Abbreviation: Metabolism Subsets: MEDLINE
أسماء مطبوعة: Publication: New York, NY : Elsevier Inc.
Original Publication: New York, Grune & Stratton.
مواضيع طبية MeSH: Basal Metabolism* , Gene Deletion*, Diet, High-Fat/*adverse effects , Obesity/*prevention & control , Pyrophosphatases/*genetics, Adipose Tissue, Brown/metabolism ; Adipose Tissue, White/metabolism ; Animals ; Animals, Genetically Modified ; Blood Glucose/metabolism ; Disease Models, Animal ; Female ; Homeostasis ; Insulin/metabolism ; Insulin-Secreting Cells/enzymology ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/etiology ; Obesity/genetics
مستخلص: Background: Ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3), also known as CD39L3, is the dominant ectonucleotidase expressed by beta cells in the islet of Langerhans and on nerves. NTPDase3 catalyzes the conversion of extracellular ATP and ADP to AMP and modulates purinergic signaling. Previous studies have shown that NTPDase3 decreases insulin release from beta-cells in vitro. This study aims to determine the impact of NTPDase3 in diet-induced obesity (DIO) and metabolism in vivo.
Methods: We developed global NTPDase3 deficient (Entpd3 -/- ) and islet beta-cell-specific NTPDase-3 deficient mice (Entpd3 flox/flox,InsCre ) using Ins1-Cre targeted gene editing to compare metabolic phenotypes with wildtype (WT) mice on a high-fat diet (HFD).
Results: Entpd3 -/- mice exhibited similar growth rates compared to WT on chow diet. When fed HFD, Entpd3 -/- mice demonstrated significant resistance to DIO. Entpd3 -/- mice consumed more calories daily and exhibited less fecal calorie loss. Although Entpd3 -/- mice had no increases in locomotor activity, the mice exhibited a significant increase in basal metabolic rate when on the HFD. This beneficial phenotype was associated with improved glucose tolerance, but not higher insulin secretion. In fact, Entpd3 flox/flox,InsCre mice demonstrated similar metabolic phenotypes and insulin secretion compared to matched controls, suggesting that the expression of NTPDase3 in beta-cells was not the primary protective factor. Instead, we observed a higher expression of uncoupling protein 1 (UCP-1) in brown adipose tissue and an augmented browning in inguinal white adipose tissue with upregulation of UCP-1 and related genes involved in thermogenesis in Entpd3 -/- mice.
Conclusions: Global NTPDase3 deletion in mice is associated with resistance to DIO and obesity-associated glucose intolerance. This outcome is not driven by the expression of NTPDase3 in pancreatic beta-cells, but rather likely mediated through metabolic changes in adipocytes.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest relevant to this study.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: K08 DK115883 United States DK NIDDK NIH HHS; R21 AG065923 United States AG NIA NIH HHS; PJT-156205 Canada CIHR; R01 HL094400 United States HL NHLBI NIH HHS; R21 CA221702 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Adipose tissue; Ectonucleotidase; Insulin resistance; NTPDase3; Obesity; Purinergic signaling
المشرفين على المادة: 0 (Blood Glucose)
0 (Insulin)
EC 3.6.1.- (Pyrophosphatases)
EC 3.6.1.- (nucleoside-triphosphate diphosphohydrolase 3)
تواريخ الأحداث: Date Created: 20210225 Date Completed: 20210527 Latest Revision: 20220510
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8052311
DOI: 10.1016/j.metabol.2021.154731
PMID: 33631144
قاعدة البيانات: MEDLINE
الوصف
تدمد:1532-8600
DOI:10.1016/j.metabol.2021.154731