Effects of Obesity on Autophagy and mTORC1 Signalling in Skeletal Muscle

NCT07774676 | Recruiting

• 1 other identifier: RG_25-084
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Overweight; Obesity; Skeletal muscle; Autophagy; mTORC1 signalling; Protein metabolism

Outcome Measures

Primary Outcomes (1)

• mTORC1-lysosomal translocation

  The translocation of the mTORC1-lysosomal complex toward the cell periphery following resistance exercise and/or protein ingestion will be assessed in skeletal muscle cross sections via immunofluorescence microscopy.

  From completion of experimental testing/biosample collection until end of study, an average of 1 year.

Secondary Outcomes (3)

• mTORC1 activation

  From completion of experimental testing/biosample collection until end of study, an average of 1 year.

• Autophagic Flux

  From completion of experimental testing/biosample collection until end of study, an average of 1 year.

• Lysosomal Content

  From completion of experimental testing/biosample collection until end of study, an average of 1 year.

Other Outcomes (2)

• Circulating Amino Acids Concentrations

  From completion of experimental testing/biosample collection until end of study, an average of 1 year.

• Circulating Hormone Concentrations

  From completion of experimental testing/biosample collection until end of study, an average of 1 year.

Study Arms (2)

Lean Individuals

This cohort will be aged between 18-45yrs and have a Body Mass index (BMI) of 18.5-25.9kg/m2. They will also have been weight-stable (\<5% bodyweight change in previous 6 months).

Procedure: Skeletal muscle biopsy; Procedure: venous blood sampling; Dietary Supplement: Protein-Rich Beverage; Other: Single-leg resistance exercise; Radiation: Dual-Energy X-ray Absorptiometry (DEXA) Scan; Other: Maximal Strength Testing

Individuals with Overweight or Obesity

This cohort will be aged between 18-45yrs and have a Body Mass index (BMI) of \>28kg/m2. They will also have been weight-stable (\<5% bodyweight change in previous 6 months).

Procedure: Skeletal muscle biopsy; Procedure: venous blood sampling; Dietary Supplement: Protein-Rich Beverage; Other: Single-leg resistance exercise; Radiation: Dual-Energy X-ray Absorptiometry (DEXA) Scan; Other: Maximal Strength Testing

Interventions

Skeletal muscle biopsy PROCEDURE

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.

Individuals with Overweight or Obesity; Lean Individuals

venous blood sampling PROCEDURE

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.

Individuals with Overweight or Obesity; Lean Individuals

Protein-Rich Beverage DIETARY_SUPPLEMENT

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).

Individuals with Overweight or Obesity; Lean Individuals

Single-leg resistance exercise OTHER

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.

Individuals with Overweight or Obesity; Lean Individuals

Dual-Energy X-ray Absorptiometry (DEXA) Scan RADIATION

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.

Individuals with Overweight or Obesity; Lean Individuals

Maximal Strength Testing OTHER

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.

Also known as: 1RM testing

Individuals with Overweight or Obesity; Lean Individuals

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Cis-gender males and females
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from around the West Midlands area via recruitment media.

You may qualify if:

• Age - 18-45yrs
• BMI - 18.5-24.9kg/m2 OR \>28kg/m2 (self-declaration, or calculated by research team based on height and weight)
• Weight Stable i.e. no change in weight of more than 5% in previous 6 months
• Meeting UK Physical activity guidelines (150 mins moderate or 75 mins vigorous activity/wk)
• Not involved in structured exercise training in previous 6 months
• No other diagnosed metabolic or neuromuscular conditions (self-declaration)

You may not qualify if:

• Currently using anti-diabetes medication (insulin, metformin, sulphonylureas, meglitinides, thiazolidinediones, DPP- 4 inhibitors, GLP-1 inhibitors).
• Currently taking cholesterol lowering medications (statins)
• Currently engaged in active weight loss programmes or using weight loss medication
• Chronic kidney disease (moderate to severe reduction in kidney function), defined as eGFR \<30 ml/min/1.73m2 identified by self declaration.
• Pregnant or breast feeding
• Currently using anti-coagulation medication
• Hypothyroidism
• Type 1 diabetes
• Current or recent weakness/injury to either leg that may affect muscle function or ability to exercise
• Current gastrointestinal issue/condition that may affect digestion and absorption of protein drink
• Individuals who follow a vegan diet or have intolerance/allergies to Whey protein.
• Previous adverse reaction to local anaethetic (lidocaine or marcaine).

Sponsors & Collaborators

• University of Birmingham: lead

Study Sites (1)

School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham

Birmingham, B152TT, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Throughout the single experimental visit, 5 muscle (vastus lateralis- \~150mg per sample) samples will be collected from participants as well as 12 venous blood samples (\~8ml per sample, antecubital vein) which will be stored for subsequent biochemical analysis.

MeSH Terms

Conditions

Overweight; Obesity

Interventions

Blood Specimen Collection; Absorptiometry, Photon

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Radiography; Diagnostic Imaging; Densitometry; Photometry; Chemistry Techniques, Analytical

Study Officials

• Nathan Hodson

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Barrett, PhD

CONTACT

+447875713844; j.s.barrett@bham.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 12, 2026
• First Posted: August 19, 2026
• Study Start: April 15, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 19, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: IPD will be available upon request following publication of the IPD with no end date
• Access Criteria: Qualified researchers with an approved scientifically sound research proposal from recognized academic, clinical, or commercial institutions can request IPD from the principal investigator. In such cases, the de-identified data long with the study protocol will be provided via a secure cloud-based research environment.

Locations

GB (1)