Effects of Obesity on Autophagy and mTORC1 Signalling in Skeletal Muscle
2026年8月17日 更新者：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.
研究概览
地位
招聘中
条件
详细说明
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.
研究类型
观察性的
注册 (估计的)
24
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习联系方式
- 姓名：Jennifer Barrett, PhD
- 电话号码：+447875713844
- 邮箱：j.s.barrett@bham.ac.uk
学习地点
-
-
-
Birmingham、英国、B152TT
- 招聘中
- School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham
-
接触：
- Jennifer Barrett, PhD
- 电话号码：+447875713844
- 邮箱：j.s.barrett@bham.ac.uk
-
接触：
-
首席研究员：
- Nathan Hodson, PhD
-
副研究员：
- Jennifer Barrett, PhD
-
副研究员：
- Jordan Acheson, MSc
-
-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
接受健康志愿者
是的
取样方法
非概率样本
研究人群
Participants will be recruited from around the West Midlands area via recruitment media.
描述
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).
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
|
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.
其他名称：
|
|
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.
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
mTORC1-lysosomal translocation
大体时间：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.
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
mTORC1 activation
大体时间：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
大体时间：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.
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From completion of experimental testing/biosample collection until end of study, an average of 1 year.
|
|
Lysosomal Content
大体时间：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.
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Circulating Amino Acids Concentrations
大体时间：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
大体时间：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.
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Nathan Hodson、University of Birmingham
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2026年4月15日
初级完成 (估计的)
2026年12月1日
研究完成 (估计的)
2027年12月1日
研究注册日期
首次提交
2026年8月12日
首先提交符合 QC 标准的
2026年8月17日
首次发布 (实际的)
2026年8月19日
研究记录更新
最后更新发布 (实际的)
2026年8月19日
上次提交的符合 QC 标准的更新
2026年8月17日
最后验证
2026年8月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- RG_25-084
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
是的
IPD 计划说明
IPD used in publications arising from the project will be shared upon request
IPD 共享时间框架
IPD will be available upon request following publication of the IPD with no end date
IPD 共享访问标准
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 共享支持信息类型
- 研究方案
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.