Supplementation with nitrate only modestly affects lipid and glucose metabolism in genetic and dietary-induced murine models of obesity

Abstract

To gain a better understanding of how nitrate may affect carbo hydrate and lipid metabolism, female wild type mice were fed a high fat, high fructose diet supplemented with either 0, 400, or 800 mg nitrate/kg diet for 28 days. Additionally, obese female db/db mice were fed a 5% fat diet supplemented with the same levels and source of nitrate. Nitrate decreased the sodium dependent uptake of glucose by ileal mucosa in wild type mice. Moreover, nitrate significantly decreased triglyceride content and mRNA expression levels of Pparγ in liver and Glut4 in skeletal muscle. Oral glucose tolerance as well as plasma cholesterol, triglyceride, insulin, leptin, glucose and the activity of ALT did not significantly differ between experimental groups but was higher in db/db mice than in wild type mice. Nitrate changed liver fatty acid composition and mRNA levels of Fads only slightly. Further hepatic genes encoding proteins involved in lipid and carbo hydrate metabolism were not significantly different between the three groups. Biomarkers of inflammation and autophagy in the liver were not affected by the different dietary treatments. Overall, the present data suggest that short term dietary supplementation with inorganic nitrate has only modest effects on carbohydrate and lipid metabolism in genetic and dietary induced mouse models of obesity.

Orally administered octacosanol improves some features of high fructose-induced metabolic syndrome in rats

“…( 48 ) It has also been shown that lower nitric oxide level leads to hypertriglyceridemia by lowering hepatic fatty acid oxidation and by increasing serum triglyceride level in rats fed diet containing a nitric oxide synthase inhibitor. ( 49 ) A recent report ( 50 ) has shown that short-term supplementation with nitrate, an oxidation product of nitric oxide, decreases hepatic triglyceride content in genetic and dietary-induced mouse models of obesity. ( 50 ) Therefore, a further study is needed to verify whether orally administered Oct improves triglyceride accumulation in the liver of HFD-fed rats by affecting nitric oxide synthesis and nitric oxide and nitrate levels in the tissue.…”

“…( 49 ) A recent report ( 50 ) has shown that short-term supplementation with nitrate, an oxidation product of nitric oxide, decreases hepatic triglyceride content in genetic and dietary-induced mouse models of obesity. ( 50 ) Therefore, a further study is needed to verify whether orally administered Oct improves triglyceride accumulation in the liver of HFD-fed rats by affecting nitric oxide synthesis and nitric oxide and nitrate levels in the tissue.…”

Does dietary nitrate boost the effects of caloric restriction on brain health? Potential physiological mechanisms and implications for future research

“…Caloric restriction (CR) and, more recently, an increased dietary nitrate consumption have been linked independently with several health benefits including anti-ageing effects and improvements of brain health and cognitive performance [ 8 – 10 ]. Some of the key biological mechanisms underpinning the benefits of CR and dietary nitrate on brain physiology involve the modulation of oxidative stress [ 11 – 13 ], inflammation [ 14 ], mitochondrial function [ 11 , 12 ], insulin [ 15 , 16 ], and nitric oxide signalling and autophagy [ 17 – 19 ]. This opinion paper provides a brief overview of key nutritional factors that may influence brain health, and it proposes a physiological rationale for the synergistic effects of combined CR and dietary nitrate interventions on brain health as an effective strategy for dementia risk reduction and prevention.…”

“…The locally produced NO exerts retrograde signalling to the pre-synaptic space, and this mechanism appears to be important for the consolidation of memory and learning (long-term potentiation; LTP) [ 108 , 109 ]. Dietary nitrate could induce autophagy by PPAR expression, SIRT3 and AMPK activation [ 18 , 19 ]. Studies testing the effects of dietary nitrate on glucose and insulin metabolism in animals and humans have produced mixed findings [ 12 , 16 , 110 , 111 ].…”

Assessing non-protein nitrogen sources in commercial dry dog foods

“…Thus, dietary nitrate and nitrite could be indirectly linked to improvements in vascular endothelial function and reduced blood pressure ( Carlstrom and Montenegro, 2019 ). Aside from direct effects to increase nitric oxide levels, oral or intravenous nitrate has been reported to both decrease oxidative stress and inflammatory responses in a multitude of rodent models of disease ( Cui et al, 2020 ; Hu et al, 2020 ; Peleli et al, 2020 ), whereas other studies have found no effect on inflammation ( Fischer et al, 2020 ) or have even reported increased oxidative stress ( Bruning-Fann and Kaneene, 1993 ; Mohiuddin et al, 2006 ). Beneficial effects of nitrite and urea, if any, are less clear in humans, and effects of non-protein nitrogenous compounds are virtually unknown in dogs.…”