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.
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
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.
Typ studie
Typ studie
Zápis (Odhadovaný)
Zápis
Kontakty a umístění
Studijní kontakt
Studijní kontakt
- Jméno: Jennifer Barrett, PhD
- Telefonní číslo: +447875713844
- E-mail: j.s.barrett@bham.ac.uk
Studijní místa
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Birmingham, Spojené království, B152TT
- Nábor
- School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham
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Kontakt:
- Jennifer Barrett, PhD
- Telefonní číslo: +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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Vrchní vyšetřovatel:
- Nathan Hodson, PhD
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Dílčí vyšetřovatel:
- Jennifer Barrett, PhD
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Dílčí vyšetřovatel:
- Jordan Acheson, MSc
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Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
Přijímá zdravé dobrovolníky
Metoda odběru vzorků
Studijní populace
Popis
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).
Studijní plán
Jak je studie koncipována?
Detaily designu
Počet skupin / kohort
Kohorty a intervence
Skupina / kohortaSkupina / kohorta |
Intervence / LéčbaIntervence / Léčba |
|---|---|
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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.
Ostatní jména:
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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.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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mTORC1-lysosomal translocation
Časové okno: 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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Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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mTORC1 activation
Časové okno: 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
Časové okno: 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
Časové okno: 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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Další výstupní opatření
Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Circulating Amino Acids Concentrations
Časové okno: 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
Časové okno: 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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Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Nathan Hodson, University of Birmingham
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Odhadovaný)
Primární dokončení
Dokončení studie (Odhadovaný)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Poruchy výživy
- Nadměrná výživa
- Tělesná hmotnost
- Patologické stavy, příznaky a symptomy
- Nutriční a metabolické nemoci
- Příznaky a symptomy
- Nadváha
- Obezita
- Vyšetřovací techniky
- Manipulace se vzorkem
- Klinické laboratorní techniky
- Diagnostické techniky a postupy
- Diagnóza
- Vpichy
- Chirurgické postupy, operativní
- Diagnostické zobrazování
- Techniky chemie, analytické
- Radiografie
- Denzitometrie
- Fotometrie
- Absoltiometrie, foton
- Sběr vzorků krve
Další identifikační čísla studie
Další identifikační čísla studie
- RG_25-084
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
Časový rámec sdílení IPD
Kritéria přístupu pro sdílení IPD
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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