Obesity (BMI > 35)
Conditions
Keywords
Obesity, Incretins, Skeletal muscle, Resistance training, Exercise training
Brief summary
Treatment with appetite suppressant drugs, including incretin-based receptor agonists, generally leads to clinically meaningful weight loss and reduced cardiometabolic risk. However, weight loss may include not only loss of adipose tissue but also loss of skeletal muscle mass, which ultimately may impair physical function and metabolic health. Resistance training is an effective strategy to maintain or increase skeletal muscle mass during weight loss, but its effects during treatment with appetite suppressant obesity medications have been studied insufficiently. This study will investigate whether unilateral resistance training during incretin-based receptor agonist treatment can preserve or improve skeletal muscle mass. Additionally, the study will determine whether preservation of muscle is accompanied by the preservation of muscle function and/or molecular adaptations in skeletal muscle, adipose tissue and blood. Participants will be adults with obesity who are about to start treatment with an incretin-based receptor agonist as part of routine clinical care. During the 13-week intervention, participants will perform supervised unilateral resistance training two times per week, training one leg while the other leg serves as an internal control. Data and tissue collection will take place before treatment start and after 13 weeks. Assessments include whole-body magnetic resonance imaging, blood sampling, skeletal muscle and adipose tissue biopsies, physical function tests, questionnaires, and monitoring of physical activity.
Interventions
BEHAVIORALUnilateral Resistance Training
Supervised resistance training of one leg, two sessions per week for 13 weeks, during incretin-based receptor agonist treatment. The trained leg will be randomly assigned, and the contralateral leg will serve as an internal within-participant control.
Sponsors
Karolinska Institutet
Region Stockholm
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All participants undergo incretin-based receptor agonist treatment as part of routine clinical care and complete a 13-week unilateral leg resistance training intervention. One leg is trained and the contralateral leg serves as an internal within-participant control.
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged 18-64 years with obesity. * Planned initiation of incretin-based obesity pharmacotherapy as part of routine clinical care. * Able to participate in supervised unilateral resistance training. * Able to complete physical function tests. * Able to attend study visits at the study center. * Able to provide written informed consent in the Swedish language.
Exclusion criteria
* Contraindication to magnetic resonance imaging. * Medical condition preventing resistance training or physical function testing. * Medical condition preventing skeletal muscle or adipose tissue biopsy. * Inability to understand study information in Swedish or provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Anterior Thigh Skeletal Muscle Volume | From baseline to 13 weeks | Change in skeletal muscle volume (L) of the anterior thigh muscles, measured by magnetic resonance imaging from baseline to 13 weeks. The primary comparison will be the difference in change from baseline to 13 weeks between the trained leg and the untrained contralateral leg. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in knee extension strength | From baseline to 13 weeks | Change in lower-limb muscle strength measured using isokinetic (Nm) and isometric (Nm) knee extension tests. |
| Change in muscle fatigue tolerance | From baseline to 13 weeks | Change in peak torque (Nm) during repeated maximal concentric isokinetic contractions at 180°/s, assessed over 30 repetitions. Initial peak torque will be defined as the highest peak torque recorded during the first three repetitions, and final peak torque will be defined as the mean peak torque recorded during the last five repetitions. The decline in torque-generating capacity will be calculated as the absolute and relative decrease from initial to final peak torque. |
| Change in whole-body skeletal muscle mass | From baseline to 13 weeks | Change in whole-body skeletal muscle volume (L) measured by magnetic resonance imaging. |
| Change in total body fat volume | From baseline to 13 weeks | Change in total body fat volume (L) measured by magnetic resonance imaging. |
| Change in liver fat fraction | From baseline to 13 weeks | Change in liver fat fraction (%) measured by magnetic resonance imaging. |
| Change in abdominal subcutaneous adipose tissue volume | From baseline to 13 weeks | Change in abdominal subcutaneous adipose tissue volume (L), measured by magnetic resonace imaging. |
| Change in visceral adipose tissue volume | From baseline to 13 weeks | Change in visceral adipose tissue volume (L) measured by magnetic resonance imaging. |
| Change in skeletal muscle fat fraction | From baseline to 13 weeks | Change in anterior thigh muscle fat fraction (%), measured by magnetic resonance imaging. |
Countries
Sweden
Contacts
CONTACTEric B Emanuelsson, PhD
Outcome results
None listed