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

项目摘要/摘要 在美国，儿童肥胖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团的能力 重新获得长期收益是极具挑战性的。体重和脂肪量重新增加的潜在机制 青少年肥胖的定义并不明确，这项研究将确定这一点。 肠-脑轴的神经内分泌变化(影响食欲和饱腹感)和代谢 适应(能源支出和管制的变化)已被确定为关键机制 有助于成年人减肥后体重和脂肪量的恢复。无论这些适应性反应是 是否适用于青春期青少年仍不清楚。假定成人机制适用于 儿科还为时过早，青少年会经历独特和动态的变化，例如特定的性别 发育生长和青春期驱动的荷尔蒙变化，这可能影响生物调节 能量平衡从根本上促进了脂肪堆积。 更好地了解体重增加后脂肪量回升的潜在机制 青春期丢失将推动当前治疗儿童肥胖症的范例朝着1)最优化方向发展 治疗的时机和强度，2)根据性别特定的发育特征进行量身定制的治疗， (3)引入新的干预策略。我们建议进行一项研究，以确定生物机制和 肥胖青少年(11-15岁)的健康行为导致体重和脂肪量回升 仔细考虑性别差异的影响。我们将使用既定的短期方法(8 3周)膳食替代疗法可导致体重减轻(≥体重指数降低5%)。在成功减肥之后， 我们将对个人(n=100)进行为期26周的生活方式调整治疗，预计治疗范围会很广。 从持续的体重和脂肪质量减少，保持体重和脂肪减少，以及体重的反应 脂肪块又回来了。为了检验性的影响，我们将在 基线，我们将仔细检查性别差异的生物学影响。 我们的主要结果将是通过双能x射线测量的总脂肪质量(Kg)的变化。 吸光度测定法。我们的总体假设是能量消耗、食欲和饱腹感的变化 调节荷尔蒙将独立地解释脂肪质量轨迹的可变性，并与性别相关 差异在这些关系中起着重要的调节作用。这项研究将确定新的治疗方法 通过以下方式加强肥胖青少年减肥维持的目标：1)揭示 能量调节和食欲/饱腹感激素促进脂肪量回升；2)决定性别特异性 提供量身定制的治疗方法以防止脂肪团复发的因素。

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.