ArticleDiabetologia2017
Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice.
Article in Diabetologia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 92 citations in OpenAlex.
- Review
- The association between dietary intakes of nitrate and nitrite and odds of metabolic syndrome and its component in adults.Scientific reports · 2026Article
- Gastroprotective Action of Adiponectin Against Gastric Mucosal Injury Induced by Ischemia and Reperfusion-Involvement of Nitric Oxide, Sensory Afferent Nerves, and Anti-Inflammatory Mediators.International journal of molecular sciences · 2026Article
- The association between dietary intakes of nitrate with nitrite from animal and plant food sources and the incidence of metabolic syndrome: a prospective study.Nutrition journal · 2025Article
- Excessive exposure to nitrate and nitrite boosts progression of isolated impaired fasting glucose to type 2 diabetes: a cohort study.Journal of diabetes and metabolic disorders · 2025Article
- Exposure to nitrate and nitrite disrupts cardiovascular development through estrogen receptor in zebrafish embryos and larvae.Fish physiology and biochemistry · 2024Article
- Salivary nitrate prevents osteoporosis via regulating bone marrow mesenchymal stem cells proliferation and differentiation.Journal of orthopaedic translation · 2024Article
- Alleviated cerebral infarction in male mice lacking all nitric oxide synthase isoforms after middle cerebral artery occlusion.Journal of anesthesia · 2024Article
- The Effectiveness of L-arginine in Clinical Conditions Associated with Hypoxia.International journal of molecular sciences · 2023Review
- Altered sialin mRNA gene expression in type 2 diabetic male Wistar rats: implications for nitric oxide deficiency.Scientific reports · 2023Article
- Involvement of Nitric Oxide in Protecting against Radical Species and Autoregulation of M1-Polarized Macrophages through Metabolic Remodeling.Molecules (Basel, Switzerland) · 2023Review
- Nitrate Quantification in Fresh Vegetables in Shanghai: Its Dietary Risks and Preventive Measures.International journal of environmental research and public health · 2022Article
- Superoxide Radicals in the Execution of Cell Death.Antioxidants (Basel, Switzerland) · 2022Review
- Quantitative aspects of nitric oxide production from nitrate and nitrite.EXCLI journal · 2022Review
- Nitrate Metabolism and Ischemic Cerebrovascular Disease: A Narrative Review.Frontiers in neurology · 2022Review
- Modulation of Insulin Resistance, Dyslipidemia and Serum Metabolome in iNOS Knockout Mice following Treatment with Nitrite, Metformin, Pioglitazone, and a Combination of Ampicillin and Neomycin.International journal of molecular sciences · 2021Article
- Plasma Nitrate Levels Are Related to Metabolic Syndrome and Are Not Altered by Treatment with DPP-4 Inhibitor Linagliptin: A Randomised, Placebo-Controlled Trial in Patients with Early Type 2 Diabetes Mellitus.Antioxidants (Basel, Switzerland) · 2021Article
- Article
- Control of rat muscle nitrate levels after perturbation of steady state dietary nitrate intake.Nitric oxide : biology and chemistry · 2021Article
- FOXE1 polymorphisms and chronic exposure to nitrates in drinking water cause metabolic dysfunction, thyroid abnormalities, and genotoxic damage in women.Genetics and molecular biology · 2021Article
Corrections and comments
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Authors and funding
25 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisNitric oxide (NO) is synthesised not only from L-arginine by NO synthases (NOSs), but also from its inert metabolites, nitrite and nitrate. Green leafy vegetables are abundant in nitrate, but whether or not a deficiency in dietary nitrite/nitrate spontaneously causes disease remains to be clarified. In this study, we tested our hypothesis that long-term dietary nitrite/nitrate deficiency would induce the metabolic syndrome in mice.
methodsTo this end, we prepared a low-nitrite/nitrate diet (LND) consisting of an amino acid-based low-nitrite/nitrate chow, in which the contents of L-arginine, fat, carbohydrates, protein and energy were identical with a regular chow, and potable ultrapure water. Nitrite and nitrate were undetectable in both the chow and the water.
resultsThree months of the LND did not affect food or water intake in wild-type C57BL/6J mice compared with a regular diet (RD). However, in comparison with the RD, 3 months of the LND significantly elicited visceral adiposity, dyslipidaemia and glucose intolerance. Eighteen months of the LND significantly provoked increased body weight, hypertension, insulin resistance and impaired endothelium-dependent relaxations to acetylcholine, while 22 months of the LND significantly led to death mainly due to cardiovascular disease, including acute myocardial infarction. These abnormalities were reversed by simultaneous treatment with sodium nitrate, and were significantly associated with endothelial NOS downregulation, adiponectin insufficiency and dysbiosis of the gut microbiota. CONCLUSIONS/
interpretationThese results provide the first evidence that long-term dietary nitrite/nitrate deficiency gives rise to the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice, indicating a novel pathogenetic role of the exogenous NO production system in the metabolic syndrome and its vascular complications.
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