Project Details
Description
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.
Status | Active |
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Effective start/end date | 1/1/22 → 12/31/24 |
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases: $691,847.00
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