Leptin and Adipokine Physiology

瘦素和脂肪因子生理学

• 批准号: 8138345
• 负责人: CHRISTOS S MANTZOROS
• 金额: $ 13.01万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8138345
• 关键词: Address; Adipocytes; Amenorrhea; American; Animals; Anorexia; Area; Biology; Body Weight; Body mass index; Cardiovascular Diseases; Chronic Disease; Clinical; Clinical Investigator; Clinical Medicine; Clinical Research; Cohort Studies; Colon Carcinoma; Comorbidity; Coronary heart disease; Data; Development; Diabetes Mellitus; Disease; Dyslipidemias; Eating; Energy Metabolism; Environment; Epidemic; Exercise; Explosion; Faculty; Fatty acid glycerol esters; Food Energy; Functional disorder; Funding; Goals; HIV; Health Professional; Homeostasis; Hormones; Human; Hypertension; Hypothalamic structure; Individual; Insulin Resistance; Intervention; Investigation; Laboratories; Lead; Leptin; Leptin deficiency; Leptin resistance; Link; Lipodystrophy; Maintenance; Malignant Neoplasms; Medical; Mentors; Metabolic Diseases; Metabolic syndrome; Metabolism; Mid-Career Clinical Scientist Award (K24); Molecular; Molecular Biology; Morbid Obesity; Morbidity - disease rate; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Nurses' Health Study; Obesity; Obesity associated cardiovascular disease; Outcome; Pathogenesis; Pathway interactions; Peptides; Physiology; Play; Population; Prevention; Prevention strategy; Proteins; Protocols documentation; Public Health; Recombinants; Regulation; Relative (related person); Relative Risks; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Science; Series; Signal Transduction; Stroke; Syndrome; System; Thinness; Time; Training; United States; Weight Gain; Work; adipokines; adiponectin; base; career; critical period; diabetic; effective therapy; experience; healthy volunteer; immune function; investigator training; meetings; mortality; next generation; obesity treatment; patient oriented; patient oriented research; programs; randomized placebo controlled trial; research study

DESCRIPTION (provided by applicant): The applicant has a funded research program in Leptin and Adipokine Physiology and is a Clinical Research Overseer at the BIDMC and the Joslin Diabetes Center. In addition, he has a well established track record in mentoring clinical researchers. The candidate's immediate goal is to determine the role leptin and other adipokines play in normal physiology and the pathophysiology of disease states in humans. His long-term goal is to further our understanding of adipokine biology which will eventually lead to new treatments for metabolic syndrome, diabetes, cardiovascular disease, and obesity-associated malignancies. In working towards these goals, the candidate has and will continue to be training and establishing a group of outstanding clinical investigators studying complementary aspects of energy homeostasis and metabolic disorders. A K24 award will enable the applicant to realize these goals by providing more protected time for both patient-oriented research and mentoring. The environment for this research is outstanding with many successful faculty involved in this general area of research across the Harvard Medical System. The PI has access to "state of the art" facilities in the General Clinical Research Center (GCRC) as well as ongoing large cohort studies including the Nurses Health Study and the Health Professionals Study. The indicative research protocols described herein involve the administration of recombinant human leptin in the context of GCRC-based, randomized, placebo-controlled trials, to subjects with hypothalamic amenorrhea or the HIV-associated metabolic syndrome and/or to healthy volunteers to study physiology outcomes, leptin signaling, and/or activation of hypothalamic centers by leptin in humans. Moreover, the PI is presenting some of his studies on the role of adiponectin as the link between obesity, insulin resistance and colon cancer, ranging from large observational cohort studies, to studies of human samples ex vivo, to molecular biology and mechanistic animal studies in the laboratory. The applicant is also actively participating in several other observational cohort studies as well as GCRC-based interventional studies on the treatment of obese diabetic subjects. Human obesity and its associated metabolic disorders are among the largest public health challenges of our time. Understanding the mechanisms underlying these disorders is key to finding safe and effective treatments.

描述（由申请人提供）： 申请人拥有一项受资助的瘦素和脂肪因子生理学研究项目，并且是 BIDMC 和 Joslin 糖尿病中心的临床研究监督员。此外，他在指导临床研究人员方面拥有良好的记录。候选人的近期目标是确定瘦素和其他脂肪因子在人类正常生理学和疾病状态病理生理学中所发挥的作用。他的长期目标是加深我们对脂肪因子生物学的理解，这最终将导致代谢综合征、糖尿病、心血管疾病和肥胖相关恶性肿瘤的新疗法。在实现这些目标的过程中，候选人已经并将继续培训和建立一批优秀的临床研究人员，研究能量稳态和代谢紊乱的互补方面。 K24 奖项将为申请人提供更多受保护的时间用于以患者为导向的研究和指导，从而帮助申请人实现这些目标。这项研究的环境非常优越，哈佛医学系统有许多成功的教师参与了这一一般研究领域。 PI 可以使用普通临床研究中心 (GCRC) 的“最先进”设施以及正在进行的大型队列研究，包括护士健康研究和卫生专业人员研究。本文描述的指示性研究方案涉及在基于 GCRC 的随机、安慰剂对照试验的背景下，对患有下丘脑闭经或 HIV 相关代谢综合征的受试者和/或健康志愿者施用重组人瘦素，以研究生理学结果、瘦素信号传导和/或人类瘦素对下丘脑中心的激活。此外，PI 还展示了他关于脂联素作为肥胖、胰岛素抵抗和结肠癌之间联系的作用的一些研究，范围从大型观察队列研究，到离体人体样本的研究，到分子生物学和机制动物研究。实验室。申请人还积极参与其他几项观察性队列研究以及基于 GCRC 的肥胖糖尿病受试者治疗干预研究。人类肥胖及其相关代谢紊乱是当今时代最大的公共卫生挑战之一。了解这些疾病的机制是找到安全有效的治疗方法的关键。