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: 10863048
• 负责人: Justin R. Ryder
• 金额: $ 71.63万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10863048
• 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; Disease remission; 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; 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; behavioral phenotyping; clinical care; doubly-labeled water; driving behavior; energy balance; energy efficiency; 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.

项目总结/摘要 儿童肥胖在美国是一个普遍存在的问题。虽然短期减肥可以 在高比例的肥胖青少年中实现了预防随后的体重和脂肪量的能力 长期的恢复是非常具有挑战性的。体重和脂肪量恢复的潜在机制， 肥胖青少年的定义很难确定，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（能源消耗和调节的变化）已被确定为关键机制 有助于成年人体重减轻后体重和脂肪量的恢复。这些适应性反应是否 适用于青春期的青少年仍然未知。假设成人机制适用于 儿科是过早的，青少年经历独特的动态变化，如性别特异性 发育生长和青春期驱动的激素变化，这可能会影响生物调节 能量平衡的基本方式有助于脂肪量的积累。 更好地了解体重增加后脂肪量恢复的潜在机制 在青春期的损失将推进目前的范式治疗小儿肥胖症，1）优化 治疗的时机和强度，2）基于性别特异性发育特征定制治疗， （3）引导新的干预策略。我们提出了一项研究，以确定生物机制， 健康行为驱动肥胖青少年（11至15岁）的体重和脂肪量恢复， 仔细考虑性别差异的影响。我们将使用短期的既定方法（8 周）的膳食替代疗法，以引起体重减轻（BMI降低≥5%）。成功减肥后， 我们将对接受生活方式改变治疗的个体（n=100）进行为期26周的随访， 从持续的体重和脂肪量减少，维持体重和脂肪减少， 和脂肪量恢复。为了研究性别的影响，我们将在 基线，我们将仔细研究性别特异性差异的生物学影响。 我们的主要结果将是通过双能X射线测量的总脂肪量（kg）的变化 吸收测定法我们的总体假设是，能量消耗、食欲和饱腹感的变化 调节激素将独立地解释脂肪量轨迹的变异性， 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 能量调节和食欲/饱腹感激素促进脂肪量恢复; 2）确定性别特异性 这些因素可以为定制治疗提供信息，以防止脂肪量恢复。