Chronic Inorganic Nitrate Administration Increases the Expression
of Genes Involved in the Browning of Gonadal Adipose Tissue in
Ovariectomized Rats

Nasibeh      Yousefzadeh; Sajad      Jeddi; Asghar      Ghasemi

doi:10.2174/0118715303239481231030043730

Abstract

Background and Objective: Nitrate, as nitric oxide (NO) donor, has been suggested as a nutrition-based treatment for decreasing the risk of menopause-related obesity. This study aimed to specify the effects of chronic inorganic nitrate administration on uncoupling protein-1 (UCP-1), peroxisome proliferator-activated-receptor-γ (PPAR-γ) coactivator-1α (PGC-1α), and PPAR-γ expression in gonadal adipose tissue (GAT) of ovariectomized (OVX) rats.

Methods: Female rats were assigned to 3 groups: Control, OVX, and OVX+nitrate (n=7/group), which consumed water containing inorganic nitrate (100 mg/L) for 9 months. At month 9, GAT was used for the measurement of NO metabolites (NOx), mRNA levels of NO synthases (endothelial (eNOS), inducible (iNOS), neuronal (nNOS)), and mRNA and protein levels of UCP-1, PGC-1α, and PPAR-γ.

Results: OVX rats had lower NOx concentration (45%) and eNOS (38%) and nNOS (30%) expression in GAT that was restored to normal values following nitrate administration. OVX rats had significantly lower mRNA and protein levels of UCP-1 (83% and 30%), PGC-1α (65% and 39%), and PPAR-γ (66% and 34.5%) in GAT. Chronic inorganic nitrate administration in OVXrats increased mRNA and protein levels of UCP-1 (128% and 34%), PGC-1α (115% and 43%), and PPAR-γ (236% and 38%), respectively.

Conclusion: In OVX rats, chronic nitrate administration increased gene and protein levels of UCP-1, PGC-1α, and PPAR-γ in GAT, indicating the anti-obesity effects of nitrate are partially mediated by the white adipose tissue (WAT) browning. Moreover, the stimulatory effect of inorganic nitrate on the WAT browning in OVX rats was associated with blunting the OVXinduced NO deficiency in GAT.

Keywords: Nitrate, nitric oxide, female rats, gonadal adipose tissue, browning of WAT, anti-obesity effects.

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Graphical Abstract

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DOI https://dx.doi.org/10.2174/0118715303239481231030043730	Print ISSN 1871-5303
Publisher Name Bentham Science Publisher	Online ISSN 2212-3873

Endocrine, Metabolic & Immune Disorders - Drug Targets

Chronic Inorganic Nitrate Administration Increases the Expression of Genes Involved in the Browning of Gonadal Adipose Tissue in Ovariectomized Rats

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