Influence of Obesity on Endogenous Oxalate Synthesis

肥胖对内源性草酸合成的影响

基本信息

批准号：
10265575
负责人：
ROSS P HOLMES
金额：
$ 23.84万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-21 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10265575
关键词：
Address Affect Alabama Animals Applications Grants Biochemistry Body fat Body mass index 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 diet-induced obesity dietary experimental study gastrointestinal interdisciplinary approach mouse model multidisciplinary nutrition obese person recruit response skills uptake urinary

项目摘要

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.

肥胖症和肾结石的患病率都在增加，而草酸钙是肾结石的主要成分。 70 – 80% 的结石通过尿液排出的草酸盐量是形成钙的危险因素。草酸盐结石，多项研究发现肥胖者比正常人排出更多的草酸盐体重指数正常的阿拉巴马州和德克萨斯州的肥胖率和结石病患病率都很高。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。排泄量增加的可能原因包括内源性草酸盐合成的贡献增加进入尿液草酸盐池，增强胃肠道草酸盐净吸收，并增加肾脏草酸盐我们将把 UAB 校园现有的技能和知识合并到研究中心。肥胖和草酸肾结石 (COOKS) 与 UTSW 矿物质代谢和临床中心的人员进行交流为了解决这一假设而进行的研究（CMMCR）将促进受试者招募。并增强 UAB 泌尿学、生物化学、肥胖、营养和生理学方面的技能我们的目标是确定 UTSW 的内分泌学、泌尿学、胃肠道医学/肝病学和肾病学专业。在特定目标 1 中，有助于增加肥胖草酸钙结石形成者的尿草酸盐排泄。我们将检查内源性草酸盐合成，这将是尿草酸盐的主要来源。在具体目标 2 中，我们将检查肠道和肾脏的转运过程，以确定低草酸盐饮食。胃肠道吸收和肾脏分泌草酸的贡献及其分布。还将进行测量以确定它是否与草酸盐合成或运输的成功完成相关。这些目标可能会确定减少尿草酸盐排泄和结石风险的治疗策略。这些中心的专业知识的融合应该成为未来强有力的合作研究的途径关于治疗干预。