Journal of Obesity & Weight Loss Therapy
Open Access

Abstract

Oxidative stress is a common component of obesity, being frequently present in insulin-sensitive tissues and the vasculature. However, despite much effort, it remains unclear to what extent oxidative stress contributes to obesity-associated metabolic abnormalities such as insulin resistance, steatosis/dyslipidemia and cardiovascular disease while the identities of the sources of reactive species and the allied redox-sensitive pathways that mediate the effects of oxidative stress in obesity remain elusive. Data form our laboratory have identified a substantial source of reactive species in obesity to be Xanthine Oxidoreductase (XOR) which oxidizes hypoxanthine to xanthine and xanthine to Uric Acid (UA) while reducing O2 to O2- and H2O2. This is evidenced by a significant elevation of XOR activity in both animal models of obesity and in the clinic. However, recent reports have identified XOR as a nitrite reductase and thus a source of salutary NO under conditions where dietary nitrite supplementation results in elevated nitrite levels in plasma and tissues. As such, we compared the impact of XOR inhibition versus dietary nitrite supplementation on metabolic and cardiopulmonary dysfunction in a preclinical model of diet-induced obesity. Our results demonstrate salutary outcomes from XOR inhibition; yet, the greatest benefitbeing afforded by dietary nitrite. For example, treatment with nitrite reduced oxidative stress, improved impaired glucose tolerance and diminished hemodynamic indices related to pulmonary arterial hypertension.We conclude that dietary nitrite supplementation may be a beneficial strategy to reduce both metabolic and cardiovascular dysfunction associated with obesity by altering XOR product formation from oxidants to NO.

Biography

Email: drekelley@gmail.com