title: Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice.
abstract: The metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for cardiovascular disease and type 2 diabetes. A proposed central event in metabolic syndrome is a decrease in the amount of bioavailable nitric oxide (NO) from endothelial NO synthase (eNOS). Recently, an alternative pathway for NO formation in mammals was described where inorganic nitrate, a supposedly inert NO oxidation product and unwanted dietary constituent, is serially reduced to nitrite and then NO and other bioactive nitrogen oxides. Here we show that several features of metabolic syndrome that develop in eNOS-deficient mice can be reversed by dietary supplementation with sodium nitrate, in amounts similar to those derived from eNOS under normal conditions. In humans, this dose corresponds to a rich intake of vegetables, the dominant dietary nitrate source. Nitrate administration increased tissue and plasma levels of bioactive nitrogen oxides. Moreover, chronic nitrate treatment reduced visceral fat accumulation and circulating levels of triglycerides and reversed the prediabetic phenotype in these animals. In rats, chronic nitrate treatment reduced blood pressure and this effect was also present during NOS inhibition. Our results show that dietary nitrate fuels a nitrate-nitrite-NO pathway that can partly compensate for disturbances in endogenous NO generation from eNOS. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against cardiovascular disease and type 2 diabetes.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Carlström
authors.forename: Filip J
authors.initials: FJ
authors.lastname: Larsen
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyström
authors.forename: Michael
authors.initials: M
authors.lastname: Hezel
authors.forename: Sara
authors.initials: S
authors.lastname: Borniquel
authors.forename: Eddie
authors.initials: E
authors.lastname: Weitzberg
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D019587:Dietary Supplements; D050152:Intra-Abdominal Fat / Q000187:drug effects; D024821:Metabolic Syndrome / Q000188:drug therapy*; D051379:Mice; D008817:Mice, Mutant Strains; D009566:Nitrates / Q000008:administration & dosage / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency*; D009589:Nitrogen Oxides / Q000097:blood / Q000378:metabolism; D051381:Rats; D014280:Triglycerides / Q000097:blood
chemical_list: D009566:Nitrates; D009589:Nitrogen Oxides; D014280:Triglycerides; D052250:Nitric Oxide Synthase Type III