Effects of Obesity on Autophagy and mTORC1 Signalling in Skeletal Muscle

Summary

It is well known that individuals living with overweight or obesity are not able to activate skeletal muscle growth processes to the same extent as lean individuals following activities such as weightlifting (resistance exercise) or protein ingestion. However, the underlying cell signalling pathways which may be regulating these impairments are not fully understood. This study aims to understand if skeletal muscle signalling responses to resistance exercise and protein intake differ between lean individuals and those living with overweight or obesity. The investigators will recruit a cohort of lean individuals and a cohort of individuals living with overweight/obesity who will undertake a bout of single-leg resistance exercise and consume a protein-rich drink. Before and after this, muscle samples will be obtained from each leg of participants at different timepoints to understand the effects of exercise and feeding combined (exercised leg) and feeding alone (rested leg) on different cellular processes which regulate muscle growth. This will allow the investigators to understand if their are specific pathways within skeletal muscle which could be targeted in future interventions to overcome impaired protein metabolism in those living with overweight/obesity.

Conditions

• Overweight and Obese Adults

Interventions

PROCEDURE

Skeletal muscle biopsy

On five occasions throughout the experimental visit, skeletal muscle biopsies will be obtained from the vastus lateralis of participants (3 in rested leg, 2 in exercised leg). These will be completed under local anaesthetic using the Bergstrom needle technique, modified for suction.

PROCEDURE

venous blood sampling

Upon arrival at the experimental visit, participant will have a cannula inserted into their antecubital vein for repeated blood sampling. 12 blood samples will then be taken throughout the course of the experimental trial from which both plasma and serum will be isolated.

DIETARY_SUPPLEMENT

Protein-Rich Beverage

Following completion of the acute, single-leg resistance exercise bout, participants will consumed a protein-rich beverage containing 0.25g/kg bodyweight whey protein (dissolved in 300ml water).

OTHER

Single-leg resistance exercise

During the experimental visit, participants will complete an acute bout of single-leg knee extensions on a randomised leg. This will be comprised of 6 sets of knee extensions at 80% of participants pre-determined 1 repetition maximum (1RM), with each set completed to volitional failure separated by a 2 minute rest interval.

RADIATION

Dual-Energy X-ray Absorptiometry (DEXA) Scan

During Visit 1 of the study, participants will undergo a whole-body DEXA scan to assess body composition (body fat and fate-free mass). This short, painless scan exposes participants to a small amount of radiation which is equivalent to the amount exposed to during a transatlantic flight.

OTHER

Maximal Strength Testing

During Visit 1 of the study, participants will undergo maximal knee extension strength testing using a randomised leg (which will complete exercise during experimental trial). This will involve increasing the weight on the knee extension machine until the participant can no longer complete a single repetition. This weight will then be used to calculate the workload at which the participant will complete the exercise bout during the experimental trial.

Sponsors & Collaborators

• University of Birmingham

  lead OTHER

Principal Investigators

• Nathan Hodson · University of Birmingham

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-04-15

Primary Completion

2026-12-31

Completion

2027-12-31

Countries

• United Kingdom

Study Locations