Adipokine physiology

脂肪因子生理学

基本信息

批准号：
9294048
负责人：
CHRISTOS S MANTZOROS
金额：
$ 18.08万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-15 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9294048
关键词：
Address Adipose tissue Affect Amenorrhea Area Award Biochemistry Biology Body Weight decreased Brain California Cardiovascular Diseases Career Mobility Categories Clinical Clinical Medicine Clinical Trials Cognition Communities Comorbidity Coronary heart disease Cues Development Diabetes Mellitus Dose Drug Kinetics Dyslipidemias Elderly Endocrine Glands Environment Evaluation Food Food Energy Funding Gastrointestinal tract structure Grant Guidelines Healthcare Homeostasis Hormones Human Hypertension Hypothalamic structure In Vitro Individual Industry Insulin International Intervention Juglans Lead Learning Leptin Leptin resistance Malignant Neoplasms Memory Mentors Metabolic Metabolic Diseases Metabolic syndrome Metabolism Mid-Career Clinical Scientist Award (K24)Morbidity - disease rate Muscle Mutation Non-Insulin-Dependent Diabetes Mellitus Obesity Organ Outcome Paper Pathogenesis Peer Review Pharmaceutical Preparations Phase Phase III Clinical Trials Physiological Physiology Prevalence Prospective cohort study Public Health Publishing Regulation Research Research Infrastructure Research Personnel Research Project Grants Research Training Risk Factors Role Science Scientist Series Signal Pathway Site Stroke Structure Therapeutic Therapeutic Uses Time Training United States National Institutes of Health Woman Work adipokines adiponectin analog base career clinical efficacy critical period cytokine design diabetic experience fighting glucagon-like peptide 1 improved interdisciplinary treatment approach interest leptin receptor liraglutide mortality next generation novel nutrition obesity treatment patient oriented patient oriented research relating to nervous system research and development research study response

项目摘要

The prevalence of obesity, a condition leading to several comorbidities including hypertension, dyslipidemias, coronary heart disease, stroke as well as several malignancies is on the rise in the US and worldwide leading to increasing morbidity and mortality. The mechanisms underlying the pathogenesis of obesity and associated conditions have not yet been elucidated and currently available therapeutic approaches are far from optimal. In the past few years, the scientific community realized that the adipose tissue is not an inert depot storage organ but an active endocrine organ secreting several hormones. We have thus been researching the biochemistry, physiology, pathophysiological importance and therapeutic significance of adipose tissue secreted hormones, i.e. adipokines, aiming at elucidating their function in humans. Although important and clinically useful new information has been accumulated and new compounds have been advanced to phase III clinical trials in humans (leptin, adiponectin inducing agents etc) several questions still remain. What is the role of novel adipokines? What physiological functions do they serve and how could we prove the concept of their clinical efficacy? How do they interact with other known hormones or novel, muscle secreted hormones, to alter energy homeostasis and metabolism? How could we exploit novel information to create clinical interventions to fight obesity and its complications? Addressing these and similar questions and training dedicated scientists, who by focusing on these questions will function as power multipliers, could lead to a substantial beneficial impact on clinical medicine and public health. Now an experienced mid-career clinical researcher, I have undertaken a series of patient-oriented research studies that contribute significantly towards addressing these important issues. This proposed K24 award will allow me and my mentees to continue focusing intensively on this area of research for the next five years, a critical period for the development of this field. Importantly, this K24 award will not only be expanding my potential for significant contributions in the field but will primarily be, by design of the K24 awards, the appropriate vehicle for nurturing the next generation of patient-oriented researchers in this field. The specific aims of this proposal are: 1. To provide a nourishing professional environment for the training and advancement of the careers of beginning clinical researchers, who will be conducting studies within ongoing patient-oriented research projects in the area of physiology and therapeutic use of molecules important in the regulation of energy homeostasis, and 2. To supplement already funded research projects aiming at examining the role of adipokines, gastrointestinal tract secreted molecules and myokines in metabolic diseases including obesity, diabetes and associated comorbidities. As expected based on NIH guidelines, the work performed under this K24 grant will be building upon the infrastructure provided by prospective cohort studies, pharmacokinetic studies, “proof of concept” clinical trials, and multicenter phase III-IV clinical trials already underway or planned.

肥胖症的流行，导致多种合并症，包括高血压、血脂异常、冠心病、中风以及多种恶性肿瘤在美国呈上升趋势在世界范围内导致发病率和死亡率增加的发病机制。肥胖及相关病症尚未阐明，目前可用的治疗方法在过去的几年里，科学界意识到脂肪组织并不是一个理想的组织。我们是惰性的储存器官，但却是分泌多种激素的活跃内分泌器官。研究生物化学、生理学、病理生理学的重要性和治疗意义脂肪组织分泌激素，即脂肪因子，旨在阐明它们在人类中的功能。已积累了重要且临床上有用的新信息，并已开发出新化合物进入人体 III 期临床试验（瘦素、脂联素诱导剂等）仍有几个问题新型脂肪因子的作用是什么？它们具有哪些生理功能？我们如何保留它们？证明它们的临床功效的概念如何？它们如何与其他已知的激素或新的肌肉相互作用？我们如何利用新信息来改变能量稳态和新陈代谢？制定临床干预措施来对抗肥胖及其并发症？培训专注的科学家，他们通过专注于这些问题将发挥力量倍增器的作用，可以引领对临床医学和公共卫生产生了重大的有益影响，现在是一位经验丰富的职业中期人员。作为一名临床研究员，我进行了一系列以患者为导向的研究，这些研究做出了重大贡献解决这些重要问题。拟议的 K24 奖项将使我和我的学员能够未来五年是该领域的关键时期，继续重点关注这一领域的研究重要的是，这个 K24 奖项不仅会拓展我的潜力，发挥重大作用。但根据 K24 奖项的设计，主要是培养适当的工具该提案的具体目标是： 1. 培养该领域的下一代以患者为导向的研究人员。为新人职业生涯的培训和进步提供滋养的专业环境临床研究人员，他们将在正在进行的以患者为导向的研究项目中进行研究在能量稳态调节中重要的分子的生理学和治疗用途领域，以及2。补充已资助的研究项目，旨在检查脂肪因子、胃肠道的作用代谢疾病（包括肥胖、糖尿病和相关疾病）中的道分泌分子和肌因子正如根据 NIH 指南所预期的那样，K24 拨款项下开展的工作将正在建设中。基于前瞻性队列研究、药代动力学研究、“概念验证”提供的基础设施临床试验，以及已经进行或计划进行的多中心III-IV期临床试验。