Anti-obesity and anti-diabetic effects of nitrate and nitrite

Abstract

Prevalence of obesity is increasing worldwide and type 2 diabetes to date is the most devastating complication of obesity. Decreased nitric oxide bioavailability is a feature of obesity and diabetes that links these two pathologies. Nitric oxide is synthesized both by nitric oxide synthase enzymes from l-arginine and nitric oxide synthase-independent from nitrate/nitrite. Nitric oxide production from nitrate/nitrite could potentially be used for nutrition-based therapy in obesity and diabetes. Nitric oxide deficiency also contributes to pathogeneses of cardiovascular disease and hypertension, which are associated with obesity and diabetes. This review summarizes pathways for nitric oxide production and focuses on the anti-diabetic and anti-obesity effects of the nitrate-nitrite-nitric oxide pathway. In addition to increasing nitric oxide production, nitrate and nitrite reduce oxidative stress, increase adipose tissue browning, have favorable effects on nitric oxide synthase expression, and increase insulin secretion, all effects that are potentially promising for management of obesity and diabetes. Based on current data, it could be suggested that amplifying the nitrate-nitrite-nitric oxide pathway is a diet-based strategy for increasing nitric oxide bioavailability and the management of these two interlinked conditions. Adding nitrate/nitrite to drugs that are currently used for managing diabetes (e.g. metformin) and possibly anti-obesity drugs may also enhance their efficacy.

Keywords: Insulin; Nitrate; Nitric oxide; Nitrite; Obesity; Type 2 diabetes.