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Effects of Obesity on Autophagy and mTORC1 Signalling in Skeletal Muscle

17. srpna 2026 aktualizováno: Nathan Hodson, University of Birmingham

Understanding the Effects of Obesity on Autophagic and mTORC1 Signalling Following Resistance Exercise and Protein Ingestion in Skeletal Muscle.

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.

Přehled studie

Postavení

Nábor

Podmínky

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

Pozorovací

Zápis (Odhadovaný)

24

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

Studijní místa

      • Birmingham, Spojené království, B152TT
        • Nábor
        • School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham
        • Kontakt:
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Nathan Hodson, PhD
        • Dílčí vyšetřovatel:
          • Jennifer Barrett, PhD
        • Dílčí vyšetřovatel:
          • Jordan Acheson, MSc

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

  • Dospělý

Přijímá zdravé dobrovolníky

Ano

Metoda odběru vzorků

Vzorek nepravděpodobnosti

Studijní populace

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

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

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

Kohorty a intervence

Skupina / kohorta
Intervence / Léčba
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).
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:
  • 1RM testing
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).
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:
  • 1RM testing

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
mTORC1-lysosomal translocation
Časové okno: 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.
From completion of experimental testing/biosample collection until end of study, an average of 1 year.

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
mTORC1 activation
Časové okno: 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.
From completion of experimental testing/biosample collection until end of study, an average of 1 year.
Autophagic Flux
Časové okno: 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.
From completion of experimental testing/biosample collection until end of study, an average of 1 year.
Lysosomal Content
Časové okno: 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
From completion of experimental testing/biosample collection until end of study, an average of 1 year.

Další výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Circulating Amino Acids Concentrations
Časové okno: From completion of experimental testing/biosample collection until end of study, an average of 1 year.
Amino acid concentrations will be assessed via high performance liquid chromatography to determine how much of the protein ingested arrives in circulation
From completion of experimental testing/biosample collection until end of study, an average of 1 year.
Circulating Hormone Concentrations
Časové okno: From completion of experimental testing/biosample collection until end of study, an average of 1 year.
Hormones associated with glycaemic control (glucose & insulin) will be assessed in plasma/serum samples via colorometric assay or ELISA
From completion of experimental testing/biosample collection until end of study, an average of 1 year.

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Vyšetřovatelé

  • Vrchní vyšetřovatel: Nathan Hodson, University of Birmingham

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

15. dubna 2026

Primární dokončení (Odhadovaný)

1. prosince 2026

Dokončení studie (Odhadovaný)

1. prosince 2027

Termíny zápisu do studia

První předloženo

12. srpna 2026

První předloženo, které splnilo kritéria kontroly kvality

17. srpna 2026

První zveřejněno (Aktuální)

19. srpna 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

19. srpna 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

17. srpna 2026

Naposledy ověřeno

1. srpna 2026

Více informací

Termíny související s touto studií

Další identifikační čísla studie

  • RG_25-084

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

ANO

Popis plánu IPD

IPD used in publications arising from the project will be shared upon request

Časový rámec sdílení IPD

IPD will be available upon request following publication of the IPD with no end date

Kritéria přístupu pro sdílení IPD

Qualified researchers with an approved scientifically sound research proposal from recognized academic, clinical, or commercial institutions can request IPD from the principal investigator. In such cases, the de-identified data long with the study protocol will be provided via a secure cloud-based research environment.

Typ podpůrných informací pro sdílení IPD

  • PROTOKOL STUDY

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .