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Effects of Obesity on Autophagy and mTORC1 Signalling in Skeletal Muscle

17 de agosto de 2026 atualizado por: 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.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

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.

Tipo de estudo

Observacional

Inscrição (Estimado)

24

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Locais de estudo

  • Reino Unido
      • Birmingham, Reino Unido, B152TT
        • Recrutamento
        • School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham
        • Contato:
        • Contato:
        • Investigador principal:
          • Nathan Hodson, PhD
        • Subinvestigador:
          • Jennifer Barrett, PhD
        • Subinvestigador:
          • Jordan Acheson, MSc

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto

Aceita Voluntários Saudáveis

Sim

Método de amostragem

Amostra Não Probabilística

População do estudo

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

Descrição

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).

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

Coortes e Intervenções

Grupo / Coorte
Intervenção / Tratamento
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).
Procedimento: Skeletal 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.
Procedimento: venous 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.
Suplemento dietético: Protein-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).
Outro: Single-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.
Radiação: Dual-Energy X-ray Absorptiometry (DEXA) Scan
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.
Outro: Maximal 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.
Outros nomes:
  • 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).
Procedimento: Skeletal 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.
Procedimento: venous 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.
Suplemento dietético: Protein-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).
Outro: Single-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.
Radiação: Dual-Energy X-ray Absorptiometry (DEXA) Scan
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.
Outro: Maximal 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.
Outros nomes:
  • 1RM testing

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
mTORC1-lysosomal translocation
Prazo: 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.

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
mTORC1 activation
Prazo: 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
Prazo: 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
Prazo: 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.

Outras medidas de resultado

Medida de resultado
Descrição da medida
Prazo
Circulating Amino Acids Concentrations
Prazo: 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
Prazo: 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.

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

University of Birmingham

Investigadores

  • Investigador principal: Nathan Hodson, University of Birmingham

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

15 de abril de 2026

Conclusão Primária (Estimado)

1 de dezembro de 2026

Conclusão do estudo (Estimado)

1 de dezembro de 2027

Datas de inscrição no estudo

Enviado pela primeira vez

12 de agosto de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

17 de agosto de 2026

Primeira postagem (Real)

19 de agosto de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

19 de agosto de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

17 de agosto de 2026

Última verificação

1 de agosto de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • RG_25-084

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

SIM

Descrição do plano IPD

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

Prazo de Compartilhamento de IPD

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

Critérios de acesso de compartilhamento 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.

Tipo de informação de suporte de compartilhamento de IPD

  • PROTOCOLO DE ESTUDO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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