Sugar, Uric Acid, and the Etiology of Diabetes and Obesity

  1. Miguel A. Lanaspa1
  1. 1Division of Kidney Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado
  2. 2Division of Nephrology, Eastern Colorado Health Care System, Department of Veteran Affairs, Denver, Colorado
  3. 3TMK Project, Medical Innovation Center, Kyoto University, Kyoto, Japan
  4. 4Laboratory of Renal Physiopathology and Department of Nephrology, Instituto Nacional de Cardiologia I.Ch., Mexico City, Mexico
  5. 5Renal Associates, San Antonio and Del Rio, Texas
  6. 6Division of Pediatric Gastroenterology, Children’s Hospital, Aurora, Colorado
  7. 7Division of Nephrology, Hypertension and Renal Transplantation, University of Florida, Gainesville, Florida.
  1. Corresponding author: Richard J. Johnson, richard.johnson{at}ucdenver.edu.

Abstract

The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that “a calorie is just a calorie” and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.

  • Received February 1, 2013.
  • Accepted June 17, 2013.

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