Clinical trial

Effects of Obesity on Autophagy and mTORC1 Signalling in Skeletal Muscle

Recruiting now · Not applicable · 1 countries · Registry ID NCT07774676

Recruiting nowNot applicableObservational

What this study is about

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.

A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.

Basic eligibility

Age18 Years to 45 Years
SexAll
Healthy volunteersAccepted
ConditionOverweight and Obese Adults

Full registry criteria

Inclusion Criteria: * 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) Exclusion Criteria: * 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).

Treatments and study arms

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.

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.

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).

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.

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.

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.

Primary outcomes

mTORC1-lysosomal translocationFrom completion of experimental testing/biosample collection until end of study, an average of 1 year.

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.

Study locations

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School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham🇬🇧 Birmingham, United Kingdom
Jennifer Barrett, PhDContact
Study contactContact
Nathan Hodson, PhDPrincipal Investigator