Our work focuses on how diet (and in particular fructose) as well as serum uric acid may have a role in the epidemics of obesity, diabetes, hypertension, and kidney disease. Our work includes studies in cell culture, animal models, epidemiological studies and clinical trials. Recent studies include studies of fructose induced obesity, insulin resistance, leptin resistance, and fatty liver. We also are interested in the subcellular, and especially effects on the mitochondria in response to fructose and uric acid. Most recently our work has focused on how a reduction in ATP generation in response to fructose and uric acid may translate not only into obesity, but also into fatigue and decreased exercise.
Recent experimental studies include the role of ATP depletion from fructose in the proinflammatory response, the mechanisms of urate uptake, regulation of fructokinase, and the mitochondrial effects of uric acid. We are also studying the role of NADPH oxidase in response to fructose and uric acid, mechanisms of endothelial dysfunction, and the development of leptin and insulin resistance. Clinical studies include trials to lower fructose intake or to pharmacologically reduce uric acid as a means for preventing or treating features of the metabolic syndrome.
1-2 Most Significant Publications
1) Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med 2008; 359:1811-21.
2) Johnson RJ, Perez-Pozo SE, Sautin YY, Manitius J, Sanchez-Lozada LG, Feig DI, Shafiu M, Segal M, Glassock RJ, Shimada M, Roncal C, Nakagawa T. Hypothesis: Could Excessive Fructose Intake and Uric Acid Cause Type 2 Diabetes? Endocr Rev 2009; 30: 96-116
3) Feig DI, Soletsky B, Johnson RJ. Effect of Allopurinol on the Blood Pressure of Adolescents with Newly Diagnosed Essential Hypertension. JAMA 2008;300(8):922-30
Primary Focus Area (if part of the obesity initiative)
· Obesity Pathophysiology and Disease: Applied Mechanisms.
Secondary Focus Areas (if part of the obesity initiative)
· Obesity Pathophysiology and Disease: Basic Mechanisms
· Obesity Cell Biology
Access to Specialized Populations
Benefit of CNRU
I am new to the University of Colorado, but one of the reasons I joined the faculty was to work with Groups such as those supported by CNRU. Currently I am developing collaborations with multiple groups in obesity (Jim Hill), metabolic syndrome (Robert Eckel and Jed Friedman), diabetes (Boris Draznin and David Maahs), hypertension (Stephen Daniels and Bill Hiatt), and fatty liver (Hugo Rosen, Greg Austin and Rachael McMahan).
CNRU Cores Used
Energy Balance, Metabolic,
Hill, Wyatt, Eckel, Austen, Draznin, Daniels, McMahan, Rosen, Friedman, MacLean.