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Inorganic nitrate promotes the browning of white adipose tissue through the nitrate-nitrite-nitric oxide pathway

Inorganic nitrate promotes the browning of white adipose tissue through the nitrate-nitrite-nitric oxide pathway
Inorganic nitrate promotes the browning of white adipose tissue through the nitrate-nitrite-nitric oxide pathway
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 define 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 ?-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 co-morbidity 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. Since resulting beige/brite cells exhibit anti-obesity and anti-diabetic effects, nitrate may be an effective means of inducing the browning response in adipose tissue to treat the metabolic syndrome.
0012-1797
Roberts, L.D.
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Ashmore, T.
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Kotwica, A.O.
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Murfitt, S.A.
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Fernandez, B.O.
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Feelisch, M.
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Murray, A.J.
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Griffin, J.L.
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Roberts, L.D.
771b2ed5-a7cb-483a-b220-5e1e56d591d7
Ashmore, T.
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Kotwica, A.O.
faac023a-a058-44eb-b2bf-c7ae0384181b
Murfitt, S.A.
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Fernandez, B.O.
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Feelisch, M.
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Murray, A.J.
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Griffin, J.L.
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Roberts, L.D., Ashmore, T., Kotwica, A.O., Murfitt, S.A., Fernandez, B.O., Feelisch, M., Murray, A.J. and Griffin, J.L. (2014) Inorganic nitrate promotes the browning of white adipose tissue through the nitrate-nitrite-nitric oxide pathway. Diabetes. (doi:10.2337/db14-0496).

Record type: Article

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 define 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 ?-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 co-morbidity 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. Since resulting beige/brite cells exhibit anti-obesity and anti-diabetic effects, nitrate may be an effective means of inducing the browning response in adipose tissue to treat the metabolic syndrome.

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2014 Roberts et al Diabetes Advance.pdf - Other
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Published date: 23 September 2014
Organisations: Faculty of Medicine

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Local EPrints ID: 369343
URI: http://eprints.soton.ac.uk/id/eprint/369343
ISSN: 0012-1797
PURE UUID: 45672e51-db67-4d4a-bceb-2f38b029fd91
ORCID for B.O. Fernandez: ORCID iD orcid.org/0000-0001-6337-0381
ORCID for M. Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 01 Oct 2014 12:12
Last modified: 18 Feb 2021 17:20

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Contributors

Author: L.D. Roberts
Author: T. Ashmore
Author: A.O. Kotwica
Author: S.A. Murfitt
Author: B.O. Fernandez ORCID iD
Author: M. Feelisch ORCID iD
Author: A.J. Murray
Author: J.L. Griffin

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