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.
調査の概要
状態
募集
条件
詳細な説明
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.
研究の種類
観察的
入学 (推定)
24
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Jennifer Barrett, PhD
- 電話番号：+447875713844
- メール：j.s.barrett@bham.ac.uk
研究場所
-
-
-
Birmingham、イギリス、B152TT
- 募集
- School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham
-
コンタクト：
- Jennifer Barrett, PhD
- 電話番号：+447875713844
- メール：j.s.barrett@bham.ac.uk
-
コンタクト：
-
主任研究者：
- Nathan Hodson, PhD
-
副調査官：
- Jennifer Barrett, PhD
-
副調査官：
- Jordan Acheson, MSc
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
健康ボランティアの受け入れ
はい
サンプリング方法
非確率サンプル
調査対象母集団
Participants will be recruited from around the West Midlands area via recruitment media.
説明
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).
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
|
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.
他の名前：
|
|
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.
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
mTORC1-lysosomal translocation
時間枠：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.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
mTORC1 activation
時間枠：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.
|
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Autophagic Flux
時間枠：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
時間枠：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.
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Circulating Amino Acids Concentrations
時間枠：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
時間枠：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.
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- 主任研究者：Nathan Hodson、University of Birmingham
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2026年4月15日
一次修了 (推定)
2026年12月1日
研究の完了 (推定)
2027年12月1日
試験登録日
最初に提出
2026年8月12日
QC基準を満たした最初の提出物
2026年8月17日
最初の投稿 (実際)
2026年8月19日
学習記録の更新
投稿された最後の更新 (実際)
2026年8月19日
QC基準を満たした最後の更新が送信されました
2026年8月17日
最終確認日
2026年8月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- RG_25-084
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
IPD used in publications arising from the project will be shared upon request
IPD 共有時間枠
IPD will be available upon request following publication of the IPD with no end date
IPD 共有アクセス基準
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 共有サポート情報タイプ
- STUDY_PROTOCOL
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
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