دورية أكاديمية
Adipocyte-specific Nos2 deletion improves insulin resistance and dyslipidemia through brown fat activation in diet-induced obese mice.
| العنوان: | Adipocyte-specific Nos2 deletion improves insulin resistance and dyslipidemia through brown fat activation in diet-induced obese mice. |
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| المؤلفون: | Vilela VR; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada., Samson N; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada., Nachbar R; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada., Perazza LR; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada., Lachance G; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada., Rokatoarivelo V; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada., Centano-Baez C; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada., Zancan P; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada., Sola-Penna M; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada., Bellmann K; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada., Di Marzo V; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada; Institute of Nutrition and Functional Foods, Centre NUTRISS, Université Laval, 2440 Boulevard Hochelaga Suite 1710, Québec, QC, G1V 0A6, Canada; Canada Excellence Research Chair Microbiome-Endocannabinoidome Axis in Metabolic Health (CERC-MEND), Canada., Laplante M; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada., Marette A; Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada; Institute of Nutrition and Functional Foods, Centre NUTRISS, Université Laval, 2440 Boulevard Hochelaga Suite 1710, Québec, QC, G1V 0A6, Canada. Electronic address: andre.marette@criucpq.ulaval.ca. |
| المصدر: | Molecular metabolism [Mol Metab] 2022 Mar; Vol. 57, pp. 101437. Date of Electronic Publication: 2022 Jan 14. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier GmbH Country of Publication: Germany NLM ID: 101605730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2212-8778 (Electronic) Linking ISSN: 22128778 NLM ISO Abbreviation: Mol Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [München] : Elsevier GmbH, 2012- |
| مواضيع طبية MeSH: | Dyslipidemias*/metabolism , Insulin Resistance*, Adipocytes, Brown/metabolism ; Adipose Tissue, Brown/metabolism ; Animals ; Diet, High-Fat/adverse effects ; Male ; Mice ; Mice, Knockout ; Mice, Obese ; Nitric Oxide Synthase Type II/metabolism |
| مستخلص: | Objective: Inducible nitric oxide (NO) synthase (NOS2) is a well-documented inflammatory mediator of insulin resistance in obesity. NOS2 expression is induced in both adipocytes and macrophages within adipose tissue during high-fat (HF)-induced obesity. Methods: Eight-week-old male mice with adipocyte selective deletion of the Nos2 gene (Nos2 AD-KO ) and their wildtype littermates (Nos2 fl/fl ) were subjected to chow or high-fat high-sucrose (HFHS) diet for 10 weeks followed by metabolic phenotyping and determination of brown adipose tissue (BAT) thermogenesis. The direct impact of NO on BAT mitochondrial respiration was also assessed in brown adipocytes. Results: HFHS-fed Nos2 AD-KO mice had improved insulin sensitivity as compared to Nos2 fl/fl littermates. Nos2 AD-KO mice were also protected from HF-induced dyslipidemia and exhibited increased energy expenditure compared with Nos2 fl/fl mice. This was linked to the activation of BAT in HFHS-fed Nos2 AD-KO mice as shown by increased Ucp1 and Ucp2 gene expression and augmented respiratory capacity of BAT mitochondria. Furthermore, mitochondrial respiration was inhibited by NO, or upon cytokine-induced NOS2 activation, but improved by NOS2 inhibition in brown adipocytes. Conclusions: These results demonstrate the key role of adipocyte NOS2 in the development of obesity-linked insulin resistance and dyslipidemia, partly through NO-dependent inhibition of BAT mitochondrial bioenergetics. (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.) |
| معلومات مُعتمدة: | FDN 143247 Canada CIHR |
| فهرسة مساهمة: | Keywords: Dyslipidemia; Insulin resistance; Mitochondrial respiration; Nitric oxide synthase; Obesity; brown adipose tissue |
| المشرفين على المادة: | EC 1.14.13.39 (Nitric Oxide Synthase Type II) EC 1.14.13.39 (Nos2 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20220116 Date Completed: 20220404 Latest Revision: 20220405 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8802131 |
| DOI: | 10.1016/j.molmet.2022.101437 |
| PMID: | 35033724 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 2212-8778 |
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| DOI: | 10.1016/j.molmet.2022.101437 |