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

Summary

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.

Conditions

• Obesity and Overweight

Interventions

OTHER

Incremental walking exercise on an AlterG treadmill (anti-gravity)

One visit with their current weight (BW) One visit with simulated weight loss in adolescents to determine their normal weight (NW-SBW) One visit with simulated weight loss in adolescents to determine their overweight status (OW-SBW).

Sponsors & Collaborators

• Centre Hospitalier Emile Roux

  lead OTHER

Principal Investigators

• David THIVEL Director of AME2P Laboratory - CLERMONT-FERRAND University · Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

12 Years

Max Age

16 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-12

Primary Completion

2027-02-28

Completion

2027-05-31