دورية أكاديمية
Adipocyte β-arrestin-2 is essential for maintaining whole body glucose and energy homeostasis.
العنوان: | Adipocyte β-arrestin-2 is essential for maintaining whole body glucose and energy homeostasis. |
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المؤلفون: | Pydi SP; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, NIH-20892, USA., Jain S; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, NIH-20892, USA., Tung W; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, NIH-20892, USA., Cui Y; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, NIH-20892, USA., Zhu L; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, NIH-20892, USA., Sakamoto W; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, NIH-20892, USA., Jain S; Mouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA., Abel BS; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA., Skarulis MC; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA., Liu J; Center for Molecular Medicine, National Heart, Lung, and Blood Institute, Bethesda, MD, 20892, USA., Huynh T; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20892, USA., Pacak K; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20892, USA., Caron MG; Department of Cell Biology, Duke University Medical Center, Durham, NC, 27710, USA., Gavrilova O; Mouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA., Finkel T; Center for Molecular Medicine, National Heart, Lung, and Blood Institute, Bethesda, MD, 20892, USA., Wess J; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, NIH-20892, USA. jurgenw@niddk.nih.gov. |
المصدر: | Nature communications [Nat Commun] 2019 Jul 03; Vol. 10 (1), pp. 2936. Date of Electronic Publication: 2019 Jul 03. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Intramural |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Energy Metabolism*, Adipocytes/*metabolism , Glucose/*metabolism , beta-Arrestin 2/*metabolism, Animals ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Homeostasis ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Adrenergic, beta-3/genetics ; Receptors, Adrenergic, beta-3/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; beta-Arrestin 2/genetics |
مستخلص: | β-Arrestins are major regulators of G protein-coupled receptor-mediated signaling processes. Their potential roles in regulating adipocyte function in vivo remain unexplored. Here we report the novel finding that mice lacking β-arrestin-2 (barr2) selectively in adipocytes show significantly reduced adiposity and striking metabolic improvements when consuming excess calories. We demonstrate that these beneficial metabolic effects are due to enhanced signaling through adipocyte β3-adrenergic receptors (β3-ARs), indicating that barr2 represents a potent negative regulator of adipocyte β3-AR activity in vivo. Interestingly, essentially all beneficial metabolic effects caused by adipocyte barr2 deficiency are absent in adipocyte barr2-PRDM16 double KO mice, indicating that the metabolic improvements caused by the lack of barr2 in adipocytes are mediated by the browning/beiging of white adipose tissue. Our data support the novel concept that 'G protein-biased' β3-AR agonists that do not promote β3-AR/barr2 interactions may prove useful for the treatment of obesity and related metabolic disorders. |
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المشرفين على المادة: | 0 (DNA-Binding Proteins) 0 (Prdm16 protein, mouse) 0 (Receptors, Adrenergic, beta-3) 0 (Transcription Factors) 0 (beta-Arrestin 2) IY9XDZ35W2 (Glucose) |
تواريخ الأحداث: | Date Created: 20190705 Date Completed: 20190925 Latest Revision: 20210110 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC6610117 |
DOI: | 10.1038/s41467-019-11003-4 |
PMID: | 31270323 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
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DOI: | 10.1038/s41467-019-11003-4 |