Effects of Obesity on Autophagy and mTORC1 Signalling in Skeletal Muscle
2026년 8월 17일 업데이트: 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.
연구 개요
상태
모병
정황
상세 설명
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.
연구 유형
관찰
등록 (추정된)
24
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 연락처
- 이름: Jennifer Barrett, PhD
- 전화번호: +447875713844
- 이메일: j.s.barrett@bham.ac.uk
연구 장소
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Birmingham, 영국, B152TT
- 모병
- School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham
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연락하다:
- Jennifer Barrett, PhD
- 전화번호: +447875713844
- 이메일: j.s.barrett@bham.ac.uk
-
연락하다:
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수석 연구원:
- Nathan Hodson, PhD
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부수사관:
- Jennifer Barrett, PhD
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부수사관:
- Jordan Acheson, MSc
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
- 성인
건강한 자원 봉사자를 받아들입니다
예
샘플링 방법
비확률 샘플
연구 인구
Participants will be recruited from around the West Midlands area via recruitment media.
설명
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).
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
코호트 및 개입
그룹/코호트 |
개입 / 치료 |
|---|---|
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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.
다른 이름들:
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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).
|
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.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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mTORC1-lysosomal translocation
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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mTORC1 activation
기간: 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
기간: 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
기간: 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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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Circulating Amino Acids Concentrations
기간: 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
기간: 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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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 수석 연구원: Nathan Hodson, University of Birmingham
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2026년 4월 15일
기본 완료 (추정된)
2026년 12월 1일
연구 완료 (추정된)
2027년 12월 1일
연구 등록 날짜
최초 제출
2026년 8월 12일
QC 기준을 충족하는 최초 제출
2026년 8월 17일
처음 게시됨 (실제)
2026년 8월 19일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2026년 8월 19일
QC 기준을 충족하는 마지막 업데이트 제출
2026년 8월 17일
마지막으로 확인됨
2026년 8월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- RG_25-084
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
예
IPD 계획 설명
IPD used in publications arising from the project will be shared upon request
IPD 공유 기간
IPD will be available upon request following publication of the IPD with no end date
IPD 공유 액세스 기준
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.
IPD 공유 지원 정보 유형
- 연구_프로토콜
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
아니
미국 FDA 규제 기기 제품 연구
아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .