Abstract 13141: Long-Term Dietary Nitrite and Nitrate Deficiency Causes Metabolic Syndrome-Like Phenotypes in Mice
Background: We previously reported that mice lacking all three nitric oxide (NO) synthase isoforms exhibit metabolic syndrome-like phenotypes, suggesting a crucial role of NO in preventing metabolic syndrome. It has recently been discovered that NO is produced from the NO metabolites, nitrite (NO2−) and nitrate (NO3−). NO3− is rich in green leaf vegetables, such as spinach and lettuce. Based on the background, in this study, we tested our hypothesis that long-term dietary NO2−/NO3− deficiency leads to metabolic syndrome in mice.
Method and Results: We prepared amino acid-based low NO2−/NO3− food pellets in which the contents of L-arginine, carbohydrate, protein, fat, and calorie were identical with regular food pellets. We also prepared ultrapure drinking water in which NO2−/NO3− levels were not detected. The low NO2−/NO3− food pellets plus the ultrapure drinking water (the low NO2−/NO3− diet) or regular food pellets plus tap water (the regular NO2−/NO3− diet) was administered in male wild-type C57BL/6 mice for 12 weeks (n=6-12). After the feeding, plasma NO2−/NO3− levels, plasma biochemical levels, and plasma adiponectin levels were assessed by the Griess method, colorimetric method, and enzyme-linked immunosorbent assay, respectively. The plasma NO2−/NO3− levels were markedly more reduced in the low NO2−/NO3− diet group than in the regular diet group. There were no significant differences in food intake or body weight between the two groups. Intriguingly, visceral fat weight (epididymal white adipose tissue weight), plasma total cholesterol levels, and plasma glucose levels in intraperitoneal glucose tolerance test were all significantly increased in the low NO2−/NO3− diet group as compared with the regular diet group (all P<0.05). Furthermore, plasma adiponectin levels were significantly reduced in the low NO2−/NO3− diet group compared with the regular diet group (P<0.05).
Conclusions: These results provide the first evidence that long-term dietary NO2−/NO3− deficiency causes metabolic syndrome-like phenotypes in mice, identifying the specific dietary ingredient that causes metabolic syndrome even in the absence of excess calorie intake.
Author Disclosures: M. Tsutsui: None. M. Kina-Tanada: None. T. Uchida: None. H. Kubota: None. M. Sakanashi: None. T. Matsuzaki: None. K. Noguchi: None. J. Nakasone: None. Y. Ohya: None.
- © 2014 by American Heart Association, Inc.