Influence of Obesity on Endogenous Oxalate Synthesis

肥胖对内源性草酸合成的影响

• 批准号: 10167931
• 负责人: ROSS P HOLMES
• 金额: $ 25.02万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-21 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10167931
• 关键词: Address; Affect; Alabama; Animals; Applications Grants; Biochemistry; Body fat; Calcium; Calcium Oxalate; Chemicals; Clinical Research; Collaborations; Collection; Consumption; Continuous Intravenous Infusion; Data; Development; Diet; Disease; Endocrinology; Excretory function; Fatty Liver; Fatty acid glycerol esters; Future; Glycolates; Grant; Hepatology; Incidence; Individual; Intestinal Absorption; Investigation; Joints; Kidney; Kidney Calculi; Knowledge; Laboratory Research; Lead; Leaky Gut; Liver; Macronutrients Nutrition; Measures; Medicine; Metabolic; Metabolism; Methods; Minerals; Mus; Nephrology; Obesity; Oral Administration; Oxalates; Pathway interactions; Physiological; Physiology; Plasma; Population; Prevalence; Production; Recurrence; Reporting; Research; Research Personnel; Risk; Risk Factors; Source; Southeastern United States; Techniques; Texas; Therapeutic; Therapeutic Intervention; Transport Process; United States; Universities; Urine; Urology; absorption; base; calcium intake; experimental study; gastrointestinal; interdisciplinary approach; mouse model; multidisciplinary; nutrition; recruit; response; skills; uptake; urinary

The prevalence of both obesity and kidney stones is increasing with calcium oxalate as the major component in 70 – 80% of stones. The amount of oxalate excreted in urine is a risk factor for the development of calcium oxalate stones and several studies have identified that obese individuals excrete more oxalate than individuals with normal BMI. The prevalence of both obesity and stone disease is high in both Alabama and Texas, indicating that these states are ideally suited to identify whether they are inter-related. In this project we will assess 3 possible reasons for this greater excretion including an increased contribution of endogenous oxalate synthesis to the urinary oxalate pool, enhanced net gastrointestinal oxalate absorption, and augmented renal oxalate secretion. We will merge the skill sets and knowledge present on the UAB campus in the Center for research on Obesity and Oxalate Kidney Stones (COOKS) with those in the UTSW Center for Mineral Metabolism and Clinical Research (CMMCR) in order to address this hypothesis. This joint endeavor will facilitate subject recruitment and enhance skill sets originating in urology, biochemistry, obesity, nutrition and physiology at UAB with those in endocrinology, urology, GI Medicine/hepatology and nephrology at UTSW. We aim to identify factors contributing to an increased urinary oxalate excretion in obese calcium oxalate stone formers. In Specific Aim 1 we will examine endogenous oxalate synthesis which will be the predominant source of urinary oxalate on a very low oxalate diet. In Specific Aim 2, we will examine transport processes in the gut and kidney to identify the contributions of gastrointestinal absorption and renal secretion of oxalate. Body fat content and its distribution will also be measured to determine if it correlates with oxalate synthesis or transport. The successful completion of these aims may identify therapeutic strategies that decrease urinary oxalate excretion and stone risk. The amalgamation of expertise in these Centers should be a pathway for strong future collaborative research focused on therapeutic interventions.

肥胖和肾结石的患病率都在增加，草酸钙是肾结石的主要成分。 70 - 80%的石头。尿中排出的草酸盐量是钙形成的危险因素 草酸盐结石和一些研究已经确定，肥胖的人比个人排泄更多的草酸盐 正常的BMI。肥胖和结石病的患病率在亚拉巴马和德克萨斯都很高，表明 这些状态非常适合确定它们是否相互关联。在这个项目中，我们将评估3 这种更大排泄的可能原因包括内源性草酸盐合成的贡献增加 尿草酸池，增强胃肠道草酸净吸收，增加肾草酸 分泌物我们将把UAB校园里的技能和知识合并到研究中心， 肥胖和草酸盐肾结石（COOKS）与那些在UTSW中心矿物质代谢和临床 研究（CMMCR），以解决这一假设。这一共同奋进将促进受试者招募 并提高UAB泌尿学、生物化学、肥胖、营养和生理学方面的技能， 在UTSW的内分泌学、泌尿学、GI医学/肝病学和肾病学。我们的目标是找出 导致肥胖草酸钙结石形成者尿草酸排泄增加。具体目标1 我们将研究内源性草酸盐的合成，这将是尿草酸盐的主要来源， 低草酸饮食。在具体目标2中，我们将研究肠道和肾脏中的转运过程，以确定 草酸的胃肠道吸收和肾脏分泌的贡献。体脂含量及其分布 也将被测量以确定其是否与草酸盐合成或转运相关。圆满完成 这些目标的研究可以确定减少尿草酸排泄和结石风险的治疗策略。的 这些中心的专业知识的合并应该是未来强有力的合作研究的途径， 治疗干预。