Effects of Acute Energy Deficit and Aerobic Exercise on Muscle Quality

NCT05203133 | Completed

• 1 other identifier: 21LJMUSPONSOR052
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

10 healthy, male, participants will complete a a 5-day baseline assessment (days -5 to -1) and two consecutive 5-day periods of controlled exercise to increase oxidative capacity (3 days of aerobic exercise per period, 15 kcal/kg FFM/day energy expenditure cycling) and energy intake (15 days in total, with a testing session on morning 16). This will achieve states of energy balance (EB; energy availability - EA - 45 kcal/kg of fat free mass (FFM)/day), required for weight maintenance (days 1 - 5), followed by energy deficit (ED; EA 10 kcal/kg FFM/day), required for weight loss on days 6 - 10. Over the data-collection period, participants will consume deuterium (D2O) tracer to facilitate dynamic proteomic profiling to assess the impact of the intervention on muscle quality (primary outcome measure). Muscle biopsies will therefore be collected on days -5, 1, 6 \& 11, alongside daily saliva samples, and venous blood collection on days -5, 1, 3, 5, 6, 8, 10 \& 11. These samples will be used to assess further, secondary, outcome measures including alterations in intra-muscular lipid profiles (lipid droplet content, morphology and lipid-droplet associated proteins in different subcellular compartments \[intermyofibrillar vs subsarcolemmal\]), alterations in blood metabolites and hormones and skeletal muscle glycogen concentrations. Changes in body mass, body composition and RMR will also be assessed.

Conditions

Energy Supply; Deficiency; Energy Balance; Energy Availability

Keywords

Dynamic proteomic profile; Skeletal muscle; Intra-muscular lipid profiles; Skeletal muscle glycogen; Glucose; Insulin; Leptin; Ghrelin; Testosterone; Adiponectin

Outcome Measures

Primary Outcomes (1)

• Alterations to skeletal muscle proteome

  Quantification of changes in skeletal muscle quality via dynamic proteomic profiling following short-term energy balance and energy deficit.

  Days -5, 1, 6 & 11

Secondary Outcomes (32)

• Intra-muscular lipid profile: lipid droplet content

  Days -5, 1, 6 & 11

• Intra-muscular lipid profile: lipid droplet morphology

  Days -5, 1, 6 & 11

• Intra-muscular lipid profile: lipid droplet associated proteins

  Days -5, 1, 6 & 11

• Blood metabolites/hormones: Glucose concentrations

  Days -5, 1, 3, 5, 6, 8, 10 & 11

• Blood metabolites/hormones: Insulin concentrations

  Days -5, 1, 3, 5, 6, 8, 10 & 11

Study Arms (3)

Baseline Assessment (Days -5 to -1)

EXPERIMENTAL

Participants will complete a a 5-day baseline assessment in which habitual energy intake (remote food photography method) and exercise energy expenditure will be monitored.

Dietary Supplement: Baseline Assessment

Energy Balance (Days 1 to 5)

EXPERIMENTAL

Participants will be provided with all food intake for five days, to provide an energy intake of 54 kcal/kg FFM/day. On days 1, 3 and 5, participants will complete aerobic (cycling) exercise at \~60% VO2peak to expend15 kcal/kg FFM. This will achieve a state of energy balance (energy availability = 45 kcal/kg of FFM/day, required for weight maintenance.

Dietary Supplement: Energy Balance

Energy Deficit (Days 6-11)

EXPERIMENTAL

Participants will be provided with all food intake for five days, to provide an energy intake of 19 kcal/kg FFM/day. On days 6, 8 and 10, participants will complete aerobic (cycling) exercise at \~60% VO2peak to expend15 kcal/kg FFM. This will achieve a state of energy deficit (energy availability = 10 kcal/kg of FFM/day) resulting in \~2.5 kg of weight-loss.

Dietary Supplement: Energy Deficit

Interventions

Energy Balance DIETARY_SUPPLEMENT

Energy balance phase to elicit weight-maintenance

Energy Balance (Days 1 to 5)

Energy Deficit DIETARY_SUPPLEMENT

Energy deficit phase to elicit weight-loss

Energy Deficit (Days 6-11)

Baseline Assessment DIETARY_SUPPLEMENT

Free-living assessment of energy status

Baseline Assessment (Days -5 to -1)

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Gender/Sex - Male
• Age - 18 - 40
• % body fat - \~18 - 26 %
• Health - Healthy (as determined by pre-participation questionnaires)
• Training Status - Regularly Exercising/Aerobically trained (3-4 aerobic training sessions/week, 3-5 hrs/week) Non-smokers
• Weight-stable (within 2 kg) for the past 6-months

You may not qualify if:

• Gender/Sex - Female/Other
• Age - \<18 - \>40
• Health - Deemed unable to perform exercise (assessed via readiness to exercise questionnaire)
• Current smoker.
• Medical Condition - Those with any previous diagnosis of; Osteoporosis/low bone mineral density, cardio-vascular disease, Diabetes Mellitus, Cerebrovascular Disease, blood-related illness/disorder, Asthma or other respiratory illness/disorder, Liver Disease, Kidney Disease, gastrointestinal disease, Eating Disorder or Disordered Eating.
• Those currently taking prescription medication or unwell with a cold or virus at the time of participation.
• Those unwilling to adhere to the study's methodological requirements (including adhering to alterations in diet and training - inc. alcohol abstention) from the day prior to intervention onset (24 hrs pre-intervention) to completion of follow-up assessments (day-11).
• Those following a restrictive diet (e.g. vegetarians/vegans)
• Any individuals with a food allergy/intolerance
• Training status - Does not train aerobically 3 + times/week (over past 6 months on average)

Sponsors & Collaborators

• Liverpool John Moores University: lead
• Alliance for Potato Research and Education: collaborator

Study Sites (1)

Liverpool John Moores University

Liverpool, Merseyside, L3 3AF, United Kingdom

Location

Related Publications (14)

• Areta JL, Burke LM, Camera DM, West DW, Crawshay S, Moore DR, Stellingwerff T, Phillips SM, Hawley JA, Coffey VG. Reduced resting skeletal muscle protein synthesis is rescued by resistance exercise and protein ingestion following short-term energy deficit. Am J Physiol Endocrinol Metab. 2014 Apr 15;306(8):E989-97. doi: 10.1152/ajpendo.00590.2013. Epub 2014 Mar 4.

  PMID: 24595305 BACKGROUND

• Areta JL, Hopkins WG. Skeletal Muscle Glycogen Content at Rest and During Endurance Exercise in Humans: A Meta-Analysis. Sports Med. 2018 Sep;48(9):2091-2102. doi: 10.1007/s40279-018-0941-1.

  PMID: 29923148 BACKGROUND

• Areta JL, Iraki J, Owens DJ, Joanisse S, Philp A, Morton JP, Hallen J. Achieving energy balance with a high-fat meal does not enhance skeletal muscle adaptation and impairs glycaemic response in a sleep-low training model. Exp Physiol. 2020 Oct;105(10):1778-1791. doi: 10.1113/EP088795. Epub 2020 Sep 7.

  PMID: 32820838 BACKGROUND

• Civitarese AE, Carling S, Heilbronn LK, Hulver MH, Ukropcova B, Deutsch WA, Smith SR, Ravussin E; CALERIE Pennington Team. Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med. 2007 Mar;4(3):e76. doi: 10.1371/journal.pmed.0040076.

  PMID: 17341128 BACKGROUND

• Hall KD. Body fat and fat-free mass inter-relationships: Forbes's theory revisited. Br J Nutr. 2007 Jun;97(6):1059-63. doi: 10.1017/S0007114507691946. Epub 2007 Mar 19.

  PMID: 17367567 BACKGROUND

• Hall KD, Chow CC. Estimating changes in free-living energy intake and its confidence interval. Am J Clin Nutr. 2011 Jul;94(1):66-74. doi: 10.3945/ajcn.111.014399. Epub 2011 May 11.

  PMID: 21562087 BACKGROUND

• Hammond KM, Sale C, Fraser W, Tang J, Shepherd SO, Strauss JA, Close GL, Cocks M, Louis J, Pugh J, Stewart C, Sharples AP, Morton JP. Post-exercise carbohydrate and energy availability induce independent effects on skeletal muscle cell signalling and bone turnover: implications for training adaptation. J Physiol. 2019 Sep;597(18):4779-4796. doi: 10.1113/JP278209. Epub 2019 Aug 21.

  PMID: 31364768 BACKGROUND

• Hawley JA, Morton JP. Ramping up the signal: promoting endurance training adaptation in skeletal muscle by nutritional manipulation. Clin Exp Pharmacol Physiol. 2014 Aug;41(8):608-13. doi: 10.1111/1440-1681.12246.

  PMID: 25142094 BACKGROUND

• Holwerda AM, Bouwman FG, Nabben M, Wang P, van Kranenburg J, Gijsen AP, Burniston JG, Mariman ECM, van Loon LJC. Endurance-Type Exercise Increases Bulk and Individual Mitochondrial Protein Synthesis Rates in Rats. Int J Sport Nutr Exerc Metab. 2020 Mar 1;30(2):153-164. doi: 10.1123/ijsnem.2019-0281. Epub 2020 Feb 7.

  PMID: 32035417 BACKGROUND

• Impey SG, Hearris MA, Hammond KM, Bartlett JD, Louis J, Close GL, Morton JP. Fuel for the Work Required: A Theoretical Framework for Carbohydrate Periodization and the Glycogen Threshold Hypothesis. Sports Med. 2018 May;48(5):1031-1048. doi: 10.1007/s40279-018-0867-7.

  PMID: 29453741 BACKGROUND

• Rabol R, Svendsen PF, Skovbro M, Boushel R, Haugaard SB, Schjerling P, Schrauwen P, Hesselink MK, Nilas L, Madsbad S, Dela F. Reduced skeletal muscle mitochondrial respiration and improved glucose metabolism in nondiabetic obese women during a very low calorie dietary intervention leading to rapid weight loss. Metabolism. 2009 Aug;58(8):1145-52. doi: 10.1016/j.metabol.2009.03.014. Epub 2009 Jun 18.

  PMID: 19454354 BACKGROUND

• Rhoads TW, Clark JP, Gustafson GE, Miller KN, Conklin MW, DeMuth TM, Berres ME, Eliceiri KW, Vaughan LK, Lary CW, Beasley TM, Colman RJ, Anderson RM. Molecular and Functional Networks Linked to Sarcopenia Prevention by Caloric Restriction in Rhesus Monkeys. Cell Syst. 2020 Feb 26;10(2):156-168.e5. doi: 10.1016/j.cels.2019.12.002. Epub 2020 Jan 22.

  PMID: 31982367 BACKGROUND

• Smiles WJ, Areta JL, Coffey VG, Phillips SM, Moore DR, Stellingwerff T, Burke LM, Hawley JA, Camera DM. Modulation of autophagy signaling with resistance exercise and protein ingestion following short-term energy deficit. Am J Physiol Regul Integr Comp Physiol. 2015 Sep;309(5):R603-12. doi: 10.1152/ajpregu.00413.2014. Epub 2015 Jul 1.

  PMID: 26136534 BACKGROUND

• Whytock KL, Parry SA, Turner MC, Woods RM, James LJ, Ferguson RA, Stahlman M, Boren J, Strauss JA, Cocks M, Wagenmakers AJM, Hulston CJ, Shepherd SO. A 7-day high-fat, high-calorie diet induces fibre-specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle. J Physiol. 2020 Mar;598(6):1151-1167. doi: 10.1113/JP279129. Epub 2020 Feb 14.

  PMID: 31958145 BACKGROUND

MeSH Terms

Conditions

Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Jose Areta, PhD

  Liverpool John Moores University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will complete a 5-day free-living baseline assessment period (days -5 to -1) and two consecutive 5-day periods (days 1 - 10, with a final assessment on the morning of day 11) of controlled exercise to increase oxidative capacity (3 days of aerobic exercise per period, 15 kcal/kg FFM/day energy expenditure cycling) and energy intake. This will achieve states of energy balance (EB; energy availability - EA - 45 kcal/kg of fat free mass (FFM)/day), required for weight maintenance (days 1 - 5), followed by energy deficit (ED; EA 10 kcal/kg FFM/day), required for weight loss on days 6 - 10.

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: January 24, 2022
• Study Start: August 23, 2021
• Primary Completion: December 15, 2021
• Study Completion: December 15, 2021
• Last Updated: November 9, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)