Long-term changes in weight and adipokines and the associations with genetic vari

描述（由申请人提供）：近46%的女性和33%的男性报告试图减肥。然而，体重循环-故意减轻体重，然后恢复至少10磅。- 发生在大约80%的减肥成年人身上; 50%的体重反弹发生在一年内。候选人研究的一个主要重点是行为和技术策略，以改善长期减肥的维持。在以患者为导向的研究（K24）的职业中期研究者奖的支持下，候选人将把这一重点扩大到对未能保持减肥和随后体重反弹所涉及的生物行为过程的调查。这项拟议的研究将建立在一项正在进行的随机临床试验（SMART研究）的基础上，并在24个月的行为减肥干预期间每6个月收集一次标本，以便候选人和她的多学科团队可以前瞻性地研究至少失去和恢复10磅的个体子集。在研究期间研究的三个目的是：（1）描述从基线到24个月的体重减轻和恢复模式及其对胰岛素抵抗的影响（血浆胰岛素）、脂肪因子（2）描述与能量摄入和能量消耗相关的行为，并探讨其与体重减轻和体重增加的时间关联;以及（3）探索与体重变化有关的基因变异是否与血清脂肪因子水平的变化以及与体重减轻和恢复有关的行为有关。导师计划将重点关注候选人（PI）和与她一起工作的多学科学员骨干。在K24奖的支持下，Burke博士将与一个跨学科团队合作，以提高她对体重反弹可能发生的炎症过程的认识，这可能提供肥胖，胰岛素抵抗，动脉粥样硬化和心血管疾病之间的联系;此外，她将着重于遗传学在这些生物行为过程中可能发挥的作用。她将利用她正在进行的研究指导学生，研究员和初级教师对行为干预措施的发展，在干预和测量技术的使用，临床试验的进行，以及炎症和遗传学在体重减轻和恢复中的作用。她将制定一个指导计划，遵循NINR的战略，整合生物和行为科学以改善健康，并采用新技术以改善医疗保健。拟议的研究和指导战略将放在NINR重点领域的背景下-促进健康和预防疾病，因为它解决了一个高度流行的慢性疾病-超重和肥胖。

DESCRIPTION (provided by applicant): Nearly 46% of women and 33% of men report attempts to lose weight. However, weight cycling - intentional weight loss followed by regain of at least 10Ibs. - occurs in approximately 80% of adults who lose weight; 50% of the weight regain occurs within a year. A major focus of the candidate's research is on behavioral and technological strategies to improve long-term weight loss maintenance. With the support of the Midcareer Investigator Award in Patient-Oriented Research (K24), the candidate will expand this focus to an investigation of the biobehavioral processes involved in the failure to maintain a loss and the subsequent weight regain. The proposed study will build on an ongoing randomized clinical trial (SMART study) and collect specimens every 6 months during the 24-month behavioral, weight loss intervention so that the candidate and her multidisciplinary team can prospectively study the subset of individuals who lose and regain at least 10Ibs. during the study. The study's 3 aims are: (1) describe the patterns of weight loss and regain from baseline to 24 months and their effect on insulin resistance (plasma insulin), adipokines (TNFalpha, IL-6, adiponectin, IL-10), and ghrelin and leptin; (2) describe the behaviors related to energy intake and energy expenditure and explore their temporal associations with weight loss and weight gain; and (3) explore whether variation in genes implicated in weight change are related to change in serum level of adipokines and to the behaviors related to weight loss and regain. The mentorship plan will focus on the candidate (PI) and a multidisciplinary cadre of mentees who have been working with her. With the support of the K24 Award, Dr. Burke will work with an interdisciplinary team to advance her knowledge of the inflammatory processes that may occur with weight regain, which may provide the link between obesity, insulin resistance, atherosclerosis and cardiovascular disease; additionally, she will focus on the possible role of genetics in these biobehavioral processes. She will use her ongoing studies to mentor students, fellows and junior faculty on the development of behavioral interventions, the use of technology in interventions and measurement, the conduct of clinical trials, and the role of inflammation and genetics in weight loss and regain. She will develop a mentoring program that follows NINR's strategies for integrating biological and behavioral science for better health, and adopting new technologies for better health care. The proposed study and mentoring strategies will be placed in the context of an area of NINR emphasis - promoting health and preventing disease as it addresses a highly prevalent chronic disorder - overweight and obesity.