The Importance of Nitrate-nitrite-nitric Oxide Pathway on Browning of White-Adipose Tissue in Diabetes and Obesity: A Review

Adipose tissue, both white and brown, play an important role in energy homoeostasis. These tissues contain three types of adipocytes, white, brown, and beige (brown-in-white) adipocytes. The beige adipocytes of white adipose tissue, have a white fat-like phenotype and upon stimulation change to a brown fat-like phenotype, leading to increased thermogenesis, a phenomenon called browning. Obesity, a risk factor for the development of diabetes, with an increasing prevalence worldwide, depends not only on the intake-consumption ratio of calories, but also on the ratio of white-to-brown adipose tissue. Browning of white adipose tissue in humans is associated with beneficial metabolic effects. Nitric oxide deficiency contributes to the pathogenesis of obesity and diabetes. Nitric oxide is synthesized from L-arginine by nitric oxide synthase enzymes (classic pathway) and also independently from nitric oxide synthase- (nitrate-nitrite pathway). Nitric oxide production from the nitrate-nitrite pathway could potentially be used as a nutrition-based therapy in obesity and diabetes. The aims of this review is to summarize the properties of adipose tissue browning, and also, the browning effects of the nitrate-nitrite-nitric oxide. Based on literature available, administration of nitrate and nitrite can be considered to be a new treatment for obesity and diabetes. Nitrate and nitrite increase browning of white adipocytes by increasing nitric oxide and can improve metabolism.