Obesity and Endogenous Oxalate Synthesis

肥胖与内源性草酸盐合成

基本信息

批准号：
10667784
负责人：
Kyle D Wood
金额：
$ 12.51万
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：
2018-08-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10667784
关键词：
Adult Affect Alanine-glyoxylate aminotransferase Animal Experimentation Animal Model Animals Basic Science Biochemical Biochemical Pathway Biological Assay Body fat Body mass index Calcium Calcium Oxalate Complex Crystal Formation Data Diet Disease Dual-Energy X-Ray Absorptiometry Environment Enzymes Epidemiology Etiology Excretory function Failure Fatty acid glycerol esters Funding Future Genetic Glutathione Glycolates Goals Hepatic High Fat Diet High Prevalence Human Kidney Calculi Knowledge Laboratories Lactate Dehydrogenase Link Liver Magnetic Resonance Imaging Mass Spectrum Analysis Measures Medical Mentors Metabolic Metabolic Pathway Metabolism Mus Obese Mice Obesity Obesity Epidemic Overweight Oxalates Oxidases Pathway interactions Plasma Population Prevalence Production Prospective cohort Research Research Personnel Risk Role Site Source Southeastern United States Technology Testing Thinness Tissues Training Translational Research United States United States National Institutes of Health Waist-Hip Ratio Weight Weight Gain Work aldehyde dehydrogenases base career cohort comorbidity diet-induced obesity dietary epidemiology study experience experimental study feeding glyoxylate glyoxylate reductase high body mass index human subject insight lifestyle factors mouse model obese person skills stable isotope tool urinary waist circumference

项目摘要

Project Summary/Abstract This proposal will enable advancement of my research career under the guidance, experience, and tutelage of successful and effective mentors. In addition, my research knowledge will be augmented by training in human studies, animal work and the complex metabolic analytical skills. This proposal will give me the tools necessary to become an independent investigator. Finally, the proposed study provides me the opportunity to continue my current research endeavors, specifically looking at kidney stone disease, endogenous oxalate synthesis, and the role of obesity. The prevalence of kidney stone disease linearly increased in the U.S. over the last several decades, now afflicting 10-15% of the population. The etiology of kidney stone disease is multifactorial involving lifestyle factors, genetics, diet, and environment. Multiple medical comorbidities have been linked to kidney stone disease including obesity. One component of the most common type of stone composition is oxalate, an end product of metabolism. Small increases in urinary oxalate can increase calcium oxalate crystal formation and thus stone disease. Multiple epidemiological studies have demonstrated a positive correlation between obesity and urinary oxalate excretion. Yet, little is known about the underlying reason for this increase in urinary oxalate. Urinary oxalate levels are affected by both a dietary and endogenous component and each is felt to contribute equally. Endogenous oxalate synthesis has been previously thought to occur primarily in the liver and its major source is glyoxylate. The biochemical pathways involved in oxalate production are poorly understood despite extensive research. The central hypothesis is that the increase in urinary oxalate seen in obesity is derived from increased endogenous production. Further, it is proposed that obesity influences the metabolic processes within the liver, resulting in increased oxalate synthesis. The hypotheses will be tested by pursuing two specific aims: 1) Evaluating oxalate synthesis in a lean and a diet-induced obese animal model, 2) To demonstrate that obese humans have increased endogenous oxalate synthesis on controlled diets. I will apply our laboratories expertise in controlled dietary studies in both humans and mice, and utilize complex analytical technologies, including mass spectrometry based assays. The proposed study may provide new insights regarding the role of obesity and fat distribution on endogenous oxalate production and thus calcium oxalate kidney stone disease. It will facilitate my transition into an independent and productive NIH funded investigator.

项目摘要/摘要该建议将在我的研究生涯中提高我的研究职业成功有效的导师。此外，我的研究知识将通过人类的培训来增强研究，动物工作和复杂的代谢分析技能。该建议将为我提供必要的工具成为独立研究者。最后，拟议的研究为我提供了继续我目前的研究努力，特别研究肾脏石材疾病，内源性草酸盐合成，以及肥胖的作用。在过去的几十年中折磨10-15％的人口。肾结石病的病因是涉及生活方式的多因素因素，遗传学，饮食和环境。多种医疗合并症已与肾结石有关包括肥胖症在内的疾病。最常见类型的石材成分的一个组成部分是草酸盐，末端代谢产物。小泌尿草酸盐的少量增加可以增加草酸钙晶体的形成，并且因此石头疾病。多个流行病学研究表明肥胖之间存在正相关和草酸盐排泄。然而，关于这种尿升高的根本原因知之甚少草酸盐。草酸盐水平受饮食和内源性成分的影响，每个人都有贡献同样。先前认为内源性草酸盐合成主要发生在肝脏及其主要中来源是乙二基。尽管广泛的研究。中心假设是肥胖症中观察到的草酸盐的增加是得出的来自内源性生产的增加。此外，有人提出肥胖会影响代谢过程在肝脏内，导致草酸盐合成增加。假设将通过追求两个特定的特定来检验目的：1）评估瘦肉和饮食引起的肥胖动物模型中的草酸盐合成，2）证明肥胖人类在受控饮食上增加了血氧酸盐合成。我将应用我们的实验室人类和小鼠的受控饮食研究专业知识，并利用复杂的分析技术，包括基于质谱的测定法。拟议的研究可能会提供有关肥胖和脂肪分布在内生的作用的新见解草酸盐产生，因此草酸钙肾脏石材疾病。这将有助于我向独立和生产性NIH资助的研究者。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Is It Time to Retire the Low-Oxalate Diet? No!

是时候放弃低草酸盐饮食了吗？

DOI：
10.1089/end.2021.0576
发表时间：
2021
期刊：
Journal of endourology
影响因子：
2.7
作者：
Crivelli,JosephJ;Wood,KyleD;Assimos,DeanG
通讯作者：
Assimos,DeanG

Screening for primary hyperparathyroidism in a tertiary stone clinic, a useful endeavor.

在三级结石诊所筛查原发性甲状旁腺功能亢进症是一项有益的努力。

DOI：
10.1007/s11255-020-02476-0
发表时间：
2020
期刊：
International urology and nephrology
影响因子：
2
作者：
Boyd,CarterJ;Wood,KyleD;Singh,Nikhi;Whitaker,Dustin;McGwin,Gerald;Chen,Herbert;Assimos,DeanG
通讯作者：
Assimos,DeanG

Primary hyperoxaluria type 1: time for prime time?