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Fostering patient-oriented research in cardiometabolic disease pathogenesis and prevention

促进以患者为中心的心脏代谢疾病发病机制和预防研究

基本信息

批准号：
10199013
负责人：
Ellen A Schur
金额：
$ 11.86万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-15 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10199013
关键词：
Address Ancillary Study Area Astrocytes Atherosclerosis Attention Autonomic Dysfunction Award Body Weight Body Weight decreased Body fat Body mass index Brain Brain region Cardiology Cardiometabolic Disease Cardiovascular Diseases Carotid Arteries Carotid Artery Plaques Carotid Atherosclerotic Disease Cell physiology Data Data Collection Development Diet Dietary Factors Disease Outcome Dyslipidemias Eating Educational Status Electrocardiogram Endocrinology Enrollment Epidemiology Event Faculty Fostering Framingham Heart Study Fructose Future Generations Gliosis Glucose Glucose Intolerance Goals Health High Density Lipoprotein Cholesterol Human Hypertension Hypothalamic structure Image Impairment Incidence Inflammation Inflammatory Insulin Resistance Intake Laboratories Leadership Life Style Link Literature MRI Scans Magnetic Resonance Imaging Maternal-fetal medicine Measures Medicine Mentors Mentorship Metabolic Metabolic syndrome Methodology Microglia Monitor Morbidity - disease rate Mus Neuraxis Neurobiology Non-Insulin-Dependent Diabetes Mellitus Obesity Participant Pathogenesis Patients Pediatrics Photoplethysmography Physicians Prediabetes syndrome Predisposition Prevention Prospective cohort study Reporting Research Research Personnel Risk Factors Rodent Rodent Model Role Scientist Signal Transduction Structure of nucleus infundibularis hypothalami Testing Training United States Universities Visceral fat Washington Weight Weight Gain Work bariatric surgery blood glucose regulation cardiovascular disorder risk cardiovascular risk factor cohort comorbidity diet-induced obesity dietary disorder risk energy balance experience glucose metabolism heart rate variability high risk improved insight mid-career faculty mobile computing modifiable risk mortality neuron loss next generation novel obesity in children obesity treatment offspring patient oriented patient oriented research programs prospective response risk sharing saturated fat skills successful intervention translational study

项目摘要

The overarching goal of this proposal is to facilitate mentored training of junior investigators in the conduct of high-quality patient-oriented research into cardiometabolic disease pathogenesis. The PI is an Associate Professor of Medicine at the University of Washington whose research program to date has focused on the neurobiological basis of obesity and abnormal glucose metabolism. The current proposal broadens the impact of this work to include cardiovascular disease (CVD) outcomes. The candidate has a productive track record of research mentorship of Fellows and junior faculty clinician-investigators, including K awardees, and academic leadership in promoting mentorship at the departmental level. During this award, the PI will mentor a spectrum of trainees from fields including endocrinology and metabolism, cardiology, pediatrics, and maternal-fetal medicine. The PI will take didactic courses and engage in one-on-one coaching with experienced senior investigators to build mentoring skills. The PI's research program is currently focused on translational studies of cellular processes consistent with possible damage to the primary body-weight and glucose-regulating region of the hypothalamus—the arcuate nucleus. Studies in rodent models show that diet-induced weight gain is dependent on an inflammatory cellular response, known as gliosis, within the arcuate nucleus of the hypothalamus. Gliosis progresses with continued dietary exposure, eventually showing signs of neuron loss. Importantly, gliosis is detectable in mice and humans by magnetic resonance imaging (MRI). Using MRI, the PI discovered the first evidence of hypothalamic gliosis in obese humans. The investigators have gone on to show that hypothalamic gliosis 1) is independently related to insulin resistance in humans, 2) correlates with increased levels of visceral fat, 3) is present in obese children, 4) is exacerbated in type 2 diabetes mellitus (T2D), and 5) is improved by Roux-en-Y gastric bypass surgery. Our current projects seek to determine the relationship of hypothalamic gliosis to T2D and the development of glucose intolerance as well as whether hypothalamic gliosis is reversed by obesity treatment. The proposed research extends this work to investigate the implications of hypothalamic gliosis for CVD. Aim 1 tests the relation of hypothalamic gliosis to CVD in humans. To do this, the PI and trainees will conduct an ancillary study to the Framingham Heart Study (FHS). Aim 2 uses an epidemiologic approach to examine dietary risk factors for hypothalamic gliosis within FHS. Aim 3 seeks pilot and feasibility data relating atherosclerosis via carotid imaging and autonomic dysfunction to hypothalamic gliosis. A Mentoring Aim will advance the group's methodology for assessing dietary exposure. Completion of these Aims could provide novel insights into the potential role of the central nervous system in CVD development and critical scientific rationale for future K- and R- level studies. Moreover, the proposed research provides a breadth and depth of opportunities for promising trainees to gain the experience necessary to perform high-quality patient-oriented research on cardiometabolic disease.

这项建议的首要目标是促进指导培训初级调查员的行为