Effect of Simulated Weight Loss on the Energy Cost of Locomotion in Overweight or Obese Adolescents

Brief summary (registry, in English)

Current literature suggests that part of the energy response to weight loss is not due to changes in fat mass and lean mass, but rather to a homeostatic adaptation aimed at limiting or even preventing weight loss and preserving individuals' energy reserves, an adaptation known as "adaptive thermogenesis". This phenomenon calls for a closer look at the respective contributions of metabolic and mechanical changes induced by weight variations, with greater consideration given to the recently proposed hypothesis of dual regulation of homeostatic energy balance involving both leptin-dependent and "gravitostatic" pathways . While leptin-dependent regulation of body weight has been described and reinforced several times since the 1950s, the gravitostatic conception of this regulation is more recent and hypothesizes that terrestrial animals use gravity to regulate their body weight through receptors and pathways that have not yet been identified. This regulation would involve adaptations in energy consumption based on body weight when working against gravity, involving weight detection by osteocytes in weight-bearing bones, and leading to feedback regulation of energy metabolism and body weight . Preclinical and clinical studies conducted on rodents and human participants have shown a reduction in body weight after several weeks of mechanical overload (simulating weight gain), explained by adaptations in their food intake and energy metabolism , adaptations suggested to be particularly due to the regulation of muscle mass. Interestingly, preliminary results from this group highlight specific post-weight loss energy adaptations to such simulated weight regain in adolescents with obesity, suggesting the establishment of specific mechanisms promoting weight regain. Indeed, after weight loss, energy metabolism during locomotion was explored with and without simulated weight regain, and interestingly, energy expenditure did not return to pre-weight loss values, as a potential means of preserving weight regain. More recently, the investigators team has been able to show that such mechanical simulation of weight gain in adolescents with obesity but stable weight does not lead to an increase in their energy expenditure during locomotion, further reinforcing a susceptibility to not activating energy defense mechanisms against this weight gain.Overall, these results suggest the presence of mechanisms for preserving body mass by conserving energy stores as a compensatory defense system against weight loss, while highlighting the absence of activation of these mechanisms in the context of simulated weight gain. Indeed, while the compensatory mechanisms implicated in response to weight fluctuations have thus far been nutritional in nature, these energy adaptations, if confirmed, would suggest an upstream activation mechanism, particularly as a tonic signal for homeostatic control. It seems necessary to study in greater depth the energy adaptations to weight variations in young people with obesity, both metabolic and mechanical, in order to better understand the control of their energy balance and the mechanisms involved, which corresponds to the objectives of this project. The objective of this project is therefore to study energy adaptations (energy cost and use of energy substrates) to simulated weight loss during incremental walking exercise. Adolescents with obesity will perform a walking exercise on an AlterG (anti-gravity) treadmill, first without and then with a simulated weight loss that places them in the overweight or normal weight category.

What you commit to

• Study type: Interventional
• Planned participants: 20
• From 12 Sept 2025 to the primary completion date, 28 Feb 2027
• No sites listed in no country
• Visits and tests: ask the trial team, the registry does not list them

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Who cannot take part

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Who the study is looking for

Age in the registry: 12 years to 16 years · Sex: All · Does not accept healthy volunteers

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