Dietary Sodium Nitrate Activates Antioxidant and Mitochondrial Dynamics Genes after Moderate Intensity Acute Exercise in Metabolic Syndrome Patients.

Miguel D Ferrer,Clara Reynés,Xavier Capó,Rafael Suau,Antoni Sureda,Bartolomé Marí,Josep A Tur,Eduardo Salaberry,Magdalena Quetglas,Antoni Pons,Federica Tonolo

doi:10.3390/jcm10122618

Abstract

Exercise can induce a pro-inflammatory response in aged subjects with metabolic disorders and nitrate supplementation has shown anti-inflammatory effects. We evaluated the influence of dietary nitrate on the response of the antioxidant and mitochondrial dynamics genes to acute exercise in peripheral blood mononuclear cells (PBMCs), as well as the antioxidant and the inflammatory response of PBMCs against immune stimulation. Metabolic syndrome patients participated in a crossover study in which they consumed a beverage containing 16 mM sodium nitrate or a placebo with the same composition without nitrate before performing a submaximal test at 60–70% of their maximal heart rate for 30 min. The intake of nitrate increased the nitrate plus nitrite plasma levels about 8-fold and induced the upregulation of catalase, superoxide dismutase, glutathione peroxidase, mitofusin 2 and PGC1α in PBMCs after exercise. The gene expression of catalase and TNFα was enhanced by phorbol myristate acetate (PMA) only in the placebo group, while the glutathione peroxidase expression was enhanced by PMA only after nitrate intake. The intake of nitrate by metabolic syndrome patients induces an antioxidant and mitochondrial response to exercise at the same time that it attenuates the pro-inflammatory response to immune stimulation.

Highlights

Dietary nitrate increases the expression of anti-inflammatory markers in visceral fat and macrophages, and this is associated with the reduction of NADPH oxidasederived superoxide production in macrophages, enhancement of adipocyte mitochondrial respiration, increased protein expression of total mitochondrial complexes and elevated gene expression of uncoupling protein (UCP)-1 in mice with metabolic disfunctions
The IL6 gene expression in peripheral blood mononuclear cells (PBMCs) was significantly influenced by the presence of LPS or phorbol myristate acetate (PMA), but no significant differences between groups were observed
The present study shows that acute exercise performed in a cyclergometer by metabolic syndrome patients at 60%–70% of their maximal heart rate for about 30 min does not influence the levels of mitochondrial proteins related with antioxidant (UCP3, manganese superoxide dismutase (MnSOD)), respiratory (CoxIV) or mitochondrial remodeling (Mfn1, mitofusin 2 (Mfn2)) functions

Summary

Introduction

Dietary nitrate may have therapeutic utility against obesity and associated metabolic complications, possibly by increasing adipocyte mitochondrial respiration and by dampening inflammation and oxidative stress [3]. Animal, human and epidemiological studies have shown that dietary nitrate and nitrite modulate inflammatory processes and immune cell function and phenotypes [4,5,6,7]. Dietary nitrate increases the expression of anti-inflammatory markers in visceral fat and macrophages, and this is associated with the reduction of NADPH oxidasederived superoxide production in macrophages, enhancement of adipocyte mitochondrial respiration, increased protein expression of total mitochondrial complexes and elevated gene expression of uncoupling protein (UCP)-1 in mice with metabolic disfunctions. The potential health risks associated with the intake of nitrosamines, nitrate and nitrite in connection with endogenous nitrosation reactions have been evaluated [10]. It was concluded that there is inadequate evidence in experimental animals for the carcinogenicity of nitrate [11], while the International Agency for Research on Cancer (IARC) reviewed the carcinogenicity of nitrite and concluded that there is limited evidence in experimental animals for the carcinogenicity of nitrite per se [11]

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