Adipokine physiology

脂肪因子生理学

• 批准号: 9177787
• 负责人: CHRISTOS S MANTZOROS
• 金额: $ 18.11万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 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/9177787
• 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; Cohort Studies; 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; Public Health; Publishing; Qualifying; 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; patient oriented; patient oriented research; prospective; relating to nervous system; research and development; research study; response

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.

肥胖症患病率，这种情况导致多种合并症，包括高血压， 血脂异常，冠心病，中风以及几个在美国的症状正在上升 在全球范围内导致发病率和死亡率提高。依据的机制 肥胖和相关疾病尚未阐明，目前可用的治疗方法 远非最佳。在过去的几年中，科学界意识到脂肪组织不是 惰性仓库存储器官，但是一种活跃的内分泌器官，分泌几种激素。所以我们一直 研究生物化学，生理学，病理生理意义和治疗意义 脂肪组织分泌的恐怖，即脂肪因子，旨在阐明其在人类中的功能。虽然 重要且具有临床上有用的新信息已积累，新化合物已经 先进到人类的第三阶段临床试验（瘦素，脂联素诱导的剂等）。 保持。新颖的脂肪因子的作用是什么？他们提供什么身体功能，以及我们如何才能 证明其临床效率的概念？他们如何与其他已知马或小说，肌肉互动 分泌的恐怖，改变能量稳态和代谢？我们如何利用新颖的信息 制定临床干预措施以抵抗肥胖症及其并发症？解决这些问题和类似的问题以及 培训专门的科学家，通过专注于这些问题将起到电力乘数的作用，他们可能会领导 对临床医学和公共卫生产生重大的有益影响。现在是经验丰富的中级职业 临床研究人员，我进行了一系列面向患者的研究，这些研究显着贡献 致力于解决这些重要问题。该提议的K24奖将使我和我的Menees得以 在接下来的五年中，继续密切关注这一研究领域，这是 该领域的发展。重要的是，该K24奖不仅会扩大我的重要潜力 该领域的贡献，但主要是通过设计K24奖项，是适合培养的工具 该领域的下一代以患者为导向的研究人员。该提案的具体目的是：1。 为培训和发展开始的职业提供营养的专业环境 临床研究人员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生理学和治疗用途，以及2。 为了补充已经资助的研究项目，旨在检查脂肪因子的作用，胃肠道 肥胖，糖尿病和相关的代谢疾病中的分泌分子和肌动物。 合并症。正如基于NIH指南所预期的那样，根据这项K24赠款进行的工作将建立 关于前瞻性队列研究提供的基础设施，药代动力学研究，“概念证明” 临床试验和多中心III-IV期临床试验已经进行或计划。