Adaptive Mechanisms Responsible for Weight Regain in Youth with Obesity and the Influence of Sex

肥胖青少年体重恢复的适应性机制和性别的影响

• 批准号: 10363405
• 负责人: Justin R. Ryder
• 金额: $ 69.18万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10363405
• 关键词: 15 year old; 19 year old; Address; Adolescence; Adolescent; Adult; Automobile Driving; Behavioral; Biological; Biology; Body Weight decreased; Body mass index; Characteristics; Child; Desire for food; Development; Dietary intake; Dual-Energy X-Ray Absorptiometry; Eating Behavior; Energy Metabolism; Fatty acid glycerol esters; Female; Female Adolescents; Gastric Inhibitory Polypeptide; Gonadal Steroid Hormones; Growth; Health behavior; Homeostasis; Hormonal; Hormonal Change; Hormones; Human Development; Indirect Calorimetry; Individual; Intervention; Lead; Leptin; Life Style Modification; Longevity; Maintenance; Measures; Mediating; Metabolic; Neurosecretory Systems; Obesity; Pediatrics; Peptide YY; Phase; Physical activity; Play; Population; Prevention; Process; Protocols documentation; Puberty; Questionnaires; Regulation; Replacement Therapy; Rest; Role; Satiation; Sex Differences; Testing; United States; Weight; Work; Youth; actigraphy; base; behavioral phenotyping; clinical care; doubly-labeled water; driving behavior; energy balance; experience; ghrelin; gut-brain axis; individualized medicine; islet amyloid polypeptide; male; new therapeutic target; obesity in children; premature; preservation; prevent; primary outcome; psychosocial; public health relevance; reproductive; response; sex; success; total energy expenditure; weight maintenance

Project Summary / Abstract Pediatric obesity is a pervasive problem in the United States. While short-term weight loss can be achieved in a high proportion of adolescents with obesity the ability to prevent subsequent weight and fat mass regain long-term is extremely challenging. The mechanisms underlying weight and fat mass regain in adolescents with obesity are poorly defined and will be determined by this study. Neuroendocrine changes in the gut-brain axis (influencing appetite and satiety) and metabolic adaptation (changes in energy expenditure and regulation) have been identified as key mechanisms contributing to weight and fat mass regain after weight loss in adults. Whether these adaptive responses are applicable to pubertal adolescents remains unknown. Presuming that adult mechanisms are applicable to pediatrics is premature, adolescents undergo unique and dynamic changes, such as sex-specific developmental growth and puberty-driven hormonal alterations, which could influence the biology regulating energy balance in a fundamental way contributing to fat mass accumulation. Gaining a better understanding of the underlying mechanisms driving fat mass regain following weight loss during adolescence will advance the current paradigm for treating pediatric obesity towards, 1) optimizing the timing and intensity of treatment, 2) tailoring therapies based on sex-specific developmental characteristics, and 3) lead to new intervention strategies. We propose a study to identify the biological mechanisms and health behaviors driving weight and fat mass regain among adolescents (11 to 15 years old) with obesity by carefully considering the impact of sex-differences. We will use an established approach of short-term (8 weeks) meal replacement therapy to elicit weight loss (≥5% BMI reduction). Following successful weight loss, we will follow individuals (n=100) on lifestyle modification therapy for 26 weeks where we expect a wide-range of responses ranging from continued weight and fat mass loss, maintenance of weight and fat loss, and weight and fat mass regain. To examine the impact of sex, we will have an even distribution of males and females at baseline, and we will carefully examine the biological influence of sex-specific differences. Our primary outcome will be change in total fat mass (kg) measured by dual energy x-ray absorptiometry. Our overall hypothesis is that changes in energy expenditure and appetite and satiety regulating hormones will independently explain the variability in fat mass trajectories, with sex-specific differences playing an important role in mediating these relationships. This study will identify new treatment targets to enhance weight loss maintenance in adolescents with obesity by: 1) uncovering the key aspects of energy regulation and appetite/satiety hormones promoting fat mass regain and; 2) determining sex-specific factors to inform tailored therapies to prevent fat mass regain.

项目概要/摘要 儿童肥胖在美国是一个普遍存在的问题，而短期体重减轻是可以的。 大部分肥胖青少年能够预防随后的体重和脂肪量 长期恢复体重和脂肪量恢复的机制极具挑战性。 肥胖青少年的定义不明确，将由本研究确定。 肠脑轴的神经内分泌变化（影响食欲和饱腹感）和代谢 适应（能源支出和监管的变化）已被确定为关键机制 这些适应性反应是否有助于成人减肥后体重和脂肪量的恢复。 适用于青春期青少年的假设仍然未知。 儿科还为时过早，青少年会经历独特且动态的变化，例如性别特异性 发育生长和青春期驱动的荷尔蒙变化，这可能会影响生物调节 能量平衡从根本上促进脂肪量积累。 更好地了解体重后脂肪量恢复的潜在机制 青春期期间的损失将推动当前治疗儿童肥胖的范例：1）优化 治疗的时机和强度，2）根据性别特异性发育特征定制治疗， 3）我们提出了一项研究来确定其生物学机制和 导致肥胖青少年（11 至 15 岁）体重和脂肪量恢复的健康行为 我们将使用既定的短期方法（8）仔细考虑性别差异的影响。 周）膳食替代疗法以引起体重减轻（体重减轻≥5％）。 我们将对接受生活方式改变治疗的个体（n=100）进行为期 26 周的跟踪，我们期望获得广泛的结果 反应范围包括持续体重和脂肪量减少、维持体重和脂肪减少以及体重 为了检验性别的影响，我们将在以下时间对男性和女性进行均匀分布。 基线，我们将仔细检查性别差异的生物学影响。 我们的主要结果是通过双能 X 射线测量的总脂肪量 (kg) 的变化 我们的总体假设是能量消耗、食欲和饱腹感的变化。 调节激素将独立解释脂肪量轨迹的变异性，并且具有性别特异性 差异在调解这些关系中发挥着重要作用，这项研究将确定新的治疗方法。 目标是通过以下方式加强肥胖青少年的减肥维持：1）揭示以下关键方面 能量调节和促进脂肪量恢复的食欲/饱腹感激素；2) 确定性别特异性； 为预防脂肪量反弹的定制疗法提供信息的因素。