Effects of Obesity on Autophagy and mTORC1 Signalling in Skeletal Muscle

ConditionOverweight and Obese Adults

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18-45

SponsorUniversity of Birmingham

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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)

Disqualifiers

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.

Trial population

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

Trial design

Design model

Cohort

Time perspective

Cross-sectional

Treatments tested in this trial

Skeletal muscle biopsy
Procedure/Surgery
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/Surgery
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 intervention
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 intervention
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.

Treatment groups

24 Participants

are divided into 2 treatment groups

Group A: Lean Individuals6 interventions

Group B: Individuals with Overweight or Obesity6 interventions

Trial outcomes

Primary outcomes

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.

Time frame