Roberts, LD orcid.org/0000-0002-1455-5248, Ashmore, T, Kotwica, AO et al. (5 more authors) (2015) Inorganic Nitrate Promotes the Browning of White Adipose Tissue Through the Nitrate-Nitrite-Nitric Oxide Pathway. Diabetes, 64 (2). pp. 471-484. ISSN 0012-1797
Abstract
Inorganic nitrate was once considered an oxidation end product of nitric oxide metabolism with little biological activity. However, recent studies have demonstrated that dietary nitrate can modulate mitochondrial function in man and is effective in reversing features of the metabolic syndrome in mice. Using a combined histological, metabolomics, and transcriptional and protein analysis approach, we mechanistically defined that nitrate not only increases the expression of thermogenic genes in brown adipose tissue but also induces the expression of brown adipocyte–specific genes and proteins in white adipose tissue, substantially increasing oxygen consumption and fatty acid β-oxidation in adipocytes. Nitrate induces these phenotypic changes through a mechanism distinct from known physiological small molecule activators of browning, the recently identified nitrate-nitrite-nitric oxide pathway. The nitrate-induced browning effect was enhanced in hypoxia, a serious comorbidity affecting white adipose tissue in obese individuals, and corrected impaired brown adipocyte–specific gene expression in white adipose tissue in a murine model of obesity. Because resulting beige/brite cells exhibit antiobesity and antidiabetic effects, nitrate may be an effective means of inducing the browning response in adipose tissue to treat the metabolic syndrome.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. This is an author produced version of a paper published in Diabetes. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Dec 2018 16:33 |
Last Modified: | 07 Dec 2018 16:33 |
Status: | Published |
Publisher: | American Diabetes Association |
Identification Number: | 10.2337/db14-0496 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:138591 |