Uric Acid: A Friend in the Past, a Foe in the Present

Abstract

Abstract The etiology of the epidemics of obesity and diabetes has commonly been attributed to the western diet rich in sugars and fat. More recent studies suggest that the epidemic may have evolutionary origins. Specifically, fructose appears to be a unique nutrient that acts to reduce ATP levels in the cell, creating an alarm signal that activates an orchestrated response that includes hunger, foraging, the stimulation of fat accumulation in the adipose, liver and blood, the development of insulin resistance, a rise in blood pressure, and systemic inflammation. This constellation of findings is similar to what is called as the metabolic syndrome, but is a protective system to aid survival in settings of food shortage. Uric acid generated from ATP depletion appears to be central in driving the biologic process. Here we discuss the role of uric acid in obesity, metabolic syndrome and chronic kidney disease. A key finding is that a mutation in uric acid metabolism occurring during our past that aided survival but that today is acting as an amplifier driving the obesity response to western diet. Uric acid is emerging as a key target in the mechanisms driving metabolic syndrome and kidney disease.