Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Aug;598(16):3357-3371.
doi: 10.1113/JP279455. Epub 2020 Jun 16.

Nitrate attenuates high fat diet-induced glucose intolerance in association with reduced epididymal adipose tissue inflammation and mitochondrial reactive oxygen species emission

Henver S Brunetta  1   2 , Valerie Politis-Barber  1 , Heather L Petrick  1 , Kaitlyn M J H Dennis  1 , Aleah J Kirsh  1 , Pierre-Andre Barbeau  1 , Everson A Nunes  2 , Graham P Holloway  1
Affiliations
Free article

Nitrate attenuates high fat diet-induced glucose intolerance in association with reduced epididymal adipose tissue inflammation and mitochondrial reactive oxygen species emission

Henver S Brunetta et al. J Physiol. 2020 Aug.
Free article

Erratum in

Abstract

Key points: Dietary nitrate is a prominent therapeutic strategy to mitigate some metabolic deleterious effects related to obesity. Mitochondrial dysfunction is causally linked to adipose tissue inflammation and insulin resistance. Whole-body glucose tolerance is prevented by nitrate independent of body weight and energy expenditure. Dietary nitrate reduces epididymal adipose tissue inflammation and mitochondrial reactive oxygen species emission while preserving insulin signalling. Metabolic beneficial effects of nitrate consumption are associated with improvements in mitochondrial redox balance in hypertrophic adipose tissue.

Abstract: Evidence has accumulated to indicate that dietary nitrate alters energy expenditure and the metabolic derangements associated with a high fat diet (HFD), but the mechanism(s) of action remain incompletely elucidated. Therefore, we aimed to determine if dietary nitrate (4 mm sodium nitrate via drinking water) could prevent HFD-mediated glucose intolerance in association with improved mitochondrial bioenergetics within both white (WAT) and brown (BAT) adipose tissue in mice. HFD feeding caused glucose intolerance (P < 0.05) and increased body weight. As a result of higher body weight, energy expenditure increased proportionally. HFD-fed mice displayed greater mitochondrial uncoupling and a twofold increase in uncoupling protein 1 content within BAT. Within epididymal white adipose tissue (eWAT), HFD increased cell size (i.e. hypertrophy), mitochondrial H2 O2 emission, oxidative stress, c-Jun N-terminal kinase phosphorylation and leucocyte infiltration, and induced insulin resistance. Remarkably, dietary nitrate consumption attenuated and/or mitigated all these responses, including rendering mitochondria more coupled within BAT, and normalizing mitochondrial H2 O2 emission and insulin-mediated Akt-Thr308 phosphorylation within eWAT. Intriguingly, the positive effects of dietary nitrate appear to be independent of eWAT mitochondrial respiratory capacity and content. Altogether, these data suggest that dietary nitrate attenuates the development of HFD-induced insulin resistance in association with attenuating WAT inflammation and redox balance, independent of changes in either WAT or BAT mitochondrial respiratory capacity/content.

Keywords: insulin resistance; mitochondrial function; nitrate; nutrition; obesity.

PubMed Disclaimer

Comment in

References

    1. Alcalá M, Calderon-Dominguez M, Bustos E, Ramos P & Casals N (2017). Increased inflammation, oxidative stress and mitochondrial respiration in brown adipose tissue from obese mice. Sci Rep 22, 16082.
    1. Altintas MM, Azad A, Nayer B, Contreras G, Zaias J, Faul C, Reiser J & Nayer A (2011). Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice. J Lip Res 52, 480-488.
    1. Andrade FH, Reid MB, Allen DG & Westerblad H (1998). Effect of nitric oxide on single skeletal muscle fibres from the mouse. J Phys 509, 577-586.
    1. Appari M, Channon KM & McNeil E (2018). Metabolic regulation of adipose tissue macrophage. Antioxid Redox Signal 29, 297-313.
    1. Bal NC, Maurya SK, Sopariwala DH, Sahoo SK, Gupta SC, Shaikh SA, Pant M, Rowland LA, Bombardier E, Goonasekera SA, Tupling RA, Molkentin JD & Periasamy M (2012). Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals. Nat Med 18, 1575-1579.

Publication types

LinkOut - more resources