Influence of Obesity on Endogenous Oxalate Synthesis

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OVERALL: PROJECT SUMMARY The prevalence of both obesity and kidney stone disease has been steadily increasing in the U.S. over the past several decades. Calcium oxalate stones are the most common type including the obese cohort. There is increasing evidence that obesity is associated with increased urinary oxalate excretion, an important risk factor for calcium oxalate stone formation. To address this issue we are establishing a Center that has been given the acronym COOKS (Center for research on Obesity and Oxalate Kidney Stones). This Center, which includes a scientific research project and an administrative core with an educational enrichment program, will examine relationships between obesity and endogenous oxalate synthesis. This will be accomplished by composing a synergistic, interdisciplinary group, including scientists with a unique background in oxalate research and an obesity expert, who is a core director in the UAB Nutrition Obesity Research Center (NORC) and the Diabetic Research Center (DRC). The Center will also interact with other UAB NIH funded Centers. The results of this synergistic research effort will be utilized to generate a future competitive R01 submission and possibly a Program Project Grant. The Scientific Research project will involve a mouse model and the phenotyping of human subjects with varying degrees of obesity. Unique facilities in the NORC will be used in both models including imaging to assess body fat composition and distribution. Insulin sensitivity in the human subjects will be assessed in the DRC. The administration of a controlled low oxalate diet will be used to estimate endogenous oxalate synthesis in both models. The administration of 13C-labelled oxalate precursors will be used to assess levels of endogenous oxalate production. Our preliminary data support a direct relationship between obesity and the amount of urinary oxalate excreted derived from endogenous oxalate production. The administrative core will provide oversight of research and educational activities of COOKS. It will also be responsible for financial management, maintenance of collaborations, and communication with other pertinent NIDDK-sponsored centers and program officials. The education enrichment program will be broad based. A website will be developed to profile the centers research and accomplishments, promote educational events and disseminate information to the Urologic community and public. The data generated in these studies should increase our understanding of the relationships between obesity and endogenous oxalate synthesis and serve as a platform to develop novel therapies for stone prevention.