Effects of Obesity on Autophagy and mTORC1 Signalling in Skeletal Muscle
Understanding the Effects of Obesity on Autophagic and mTORC1 Signalling Following Resistance Exercise and Protein Ingestion in Skeletal Muscle.
Studienübersicht
Status
Status
Bedingungen
Bedingungen
Intervention / Behandlung
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Studientyp
Einschreibung (Geschätzt)
Einschreibung
Kontakte und Standorte
Studienkontakt
Studienkontakt
- Name: Jennifer Barrett, PhD
- Telefonnummer: +447875713844
- E-Mail: j.s.barrett@bham.ac.uk
Studienorte
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Birmingham, Vereinigtes Königreich, B152TT
- Rekrutierung
- School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham
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Kontakt:
- Jennifer Barrett, PhD
- Telefonnummer: +447875713844
- E-Mail: j.s.barrett@bham.ac.uk
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Kontakt:
- E-Mail: n.w.hodson@bham.ac.uk
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Hauptermittler:
- Nathan Hodson, PhD
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Unterermittler:
- Jennifer Barrett, PhD
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Unterermittler:
- Jordan Acheson, MSc
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Teilnahmekriterien
Zulassungskriterien
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
Akzeptiert gesunde Freiwillige
Probenahmeverfahren
Studienpopulation
Beschreibung
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).
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
Anzahl der Gruppen / Kohorten
Kohorten und Interventionen
Gruppe / KohorteGruppe / Kohorte |
Intervention / BehandlungIntervention / Behandlung |
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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).
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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.
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.
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).
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.
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.
Andere Namen:
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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).
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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.
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.
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).
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.
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.
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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mTORC1-lysosomal translocation
Zeitfenster: From completion of experimental testing/biosample collection until end of study, an average of 1 year.
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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.
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From completion of experimental testing/biosample collection until end of study, an average of 1 year.
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Sekundäre Ergebnismessungen
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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mTORC1 activation
Zeitfenster: From completion of experimental testing/biosample collection until end of study, an average of 1 year.
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Markers of mTORC1 activation (phosphorylation of downstream signalling targets) will be assessed via immunoblotting on homogenised skeletal muscle samples.
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From completion of experimental testing/biosample collection until end of study, an average of 1 year.
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Autophagic Flux
Zeitfenster: From completion of experimental testing/biosample collection until end of study, an average of 1 year.
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Skeletal muscle autophagic flux will be assessed on skeletal muscle samples using a novel ex vivo assay followed by immunoblotting.
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From completion of experimental testing/biosample collection until end of study, an average of 1 year.
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Lysosomal Content
Zeitfenster: From completion of experimental testing/biosample collection until end of study, an average of 1 year.
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Skeletal muscle lysosomal content will be assessed via immunoblotting for markers of the lysosome on homogenised skeletal muscle samples
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From completion of experimental testing/biosample collection until end of study, an average of 1 year.
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Andere Ergebnismessungen
Andere Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Circulating Amino Acids Concentrations
Zeitfenster: From completion of experimental testing/biosample collection until end of study, an average of 1 year.
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Amino acid concentrations will be assessed via high performance liquid chromatography to determine how much of the protein ingested arrives in circulation
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From completion of experimental testing/biosample collection until end of study, an average of 1 year.
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Circulating Hormone Concentrations
Zeitfenster: From completion of experimental testing/biosample collection until end of study, an average of 1 year.
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Hormones associated with glycaemic control (glucose & insulin) will be assessed in plasma/serum samples via colorometric assay or ELISA
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From completion of experimental testing/biosample collection until end of study, an average of 1 year.
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Mitarbeiter und Ermittler
Sponsor
Sponsor
Ermittler
Ermittler
- Hauptermittler: Nathan Hodson, University of Birmingham
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Studienbeginn
Primärer Abschluss (Geschätzt)
Primärer Abschluss
Studienabschluss (Geschätzt)
Studienabschluss
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Zuerst gepostet
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes Update gepostet
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Ernährungsstörungen
- Überernährung
- Körpergewicht
- Pathologische Zustände, Anzeichen und Symptome
- Ernährungs- und Stoffwechselerkrankungen
- Anzeichen und Symptome
- Übergewicht
- Fettleibigkeit
- Untersuchungstechniken
- Handhabung von Proben
- Klinische Labortechniken
- Diagnosetechniken und Verfahren
- Diagnose
- Punktionen
- Chirurgische Eingriffe, operativ
- Diagnostische Bildgebung
- Chemie -Techniken, analytisch
- Radiographie
- Densitometrie
- Photometrie
- Absorptiometrie, Photon
- Blutprobensammlung
Andere Studien-ID-Nummern
Andere Studien-ID-Nummern
- RG_25-084
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