Overweight and Obese Adults
Conditions
Keywords
Overweight, Obesity, Skeletal muscle, Autophagy, mTORC1 signalling, Protein metabolism
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.
Detailed description
As skeletal muscle is a major contributor to basal metabolic rate and glucose control, increasing the quality of skeletal muscle in those living with obesity could improve the long-term success of subsequent weight loss programs. There are two main activities which are often recommended to improve skeletal muscle quality, resistance exercise (i.e. weightlifting) and adequate protein intake, however, recent research has suggested that individuals living with obesity do not respond as well to these activities as a non-obese person. This research project aims to investigate if certain processes within muscle cells, which regulate muscle size and quality, are reduced in people living with obesity following a single session of resistance exercise and a protein-rich drink. This will hopefully identify processes we can target specifically to improve skeletal muscle quality. The project involves participants attending the lab and completing a session of single-leg resistance exercise and ingesting a protein drink. Before and after this the investigators will take a number of blood samples and small pieces of muscle from each thigh to understand how muscle reacts to exercise/feeding and whether this differs between individuals with and without obesity. Following the visit investigators will the conduct a variety of laboratory analysis on these samples to understand the responses. Overall, this project has the potential to help design future programmes which can improve skeletal muscle quality in those living with obesity, improving general health and increasing success of weight loss interventions. To date, the acute effects anabolic stimulation by resistance exercise and protein ingestion in individuals with obesity have been shown to be blunted. However, the mechanisms responsible for this have scarcely been investigated. We intend to build on current evidence by identifying what causes this blunted response to anabolic stimulation in individuals with obesity. This project aims to determine whether individuals with obesity exhibit differential mTORC1-lysosomal translocation in response to anabolic signaling following a single bout of resistance exercise combined with protein ingestion.
Interventions
PROCEDURESkeletal 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.
PROCEDUREvenous 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_SUPPLEMENTProtein-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).
OTHERSingle-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.
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.
OTHERMaximal 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
University of Birmingham
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| mTORC1-lysosomal translocation | From 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| mTORC1 activation | From completion of experimental testing/biosample collection until end of study, an average of 1 year. | Markers of mTORC1 activation (phosphorylation of downstream signalling targets) will be assessed via immunoblotting on homogenised skeletal muscle samples. |
| Autophagic Flux | From completion of experimental testing/biosample collection until end of study, an average of 1 year. | Skeletal muscle autophagic flux will be assessed on skeletal muscle samples using a novel ex vivo assay followed by immunoblotting. |
| Lysosomal Content | From completion of experimental testing/biosample collection until end of study, an average of 1 year. | Skeletal muscle lysosomal content will be assessed via immunoblotting for markers of the lysosome on homogenised skeletal muscle samples |
Countries
United Kingdom
Contacts
CONTACTJennifer Barrett, PhD
PRINCIPAL_INVESTIGATORNathan Hodson
University of Birmingham
Outcome results
None listed