Activating Brown Adipose Tissue Through Exercise

NCT02365129 | Unknown

• 1 other identifier: PI13/01393
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

The energy burning capacity of brown adipose tissue makes it an attractive target for anti-obesity therapies. Sympathetic nervous system (SNS) is the classical regulator of brown adipose tissue; however, recent findings show a pool of novel brown adipose tissue activators that sidestep the need for stimulating the SNS, including cardiac natriuretic peptides. Of interest is that both SNS and non-SNS brown adipose tissue activators are sensitive to physical exercise, which opens new horizons and opportunities to study the potential effect of exercise-based therapeutic interventions. Moreover, a new protein released by exercise-stimulated skeletal muscle, irisin, seems to play a key role in the browning program of white adipose tissue. Most of the available evidence comes from animal studies, which is sometimes difficult to infer to human physiology. The overall objective of the ACTIBATE randomized controlled trial is to study the effect of long-term exercise training (6 months) on brown adipose tissue activity and quantity (primary outcomes) in young overweight and obese adults. The clinical significance of activating and recruiting brown adipose tissue on resting metabolic rate and cardiometabolic profile in humans will be determined. The investigators will also study at the molecular level the benefits of exercise on the regulation pathways in two different tissues: white adipose tissue and skeletal muscle, as well as identifying possible cross-talk between the exercising muscle and heart, and fat. Information from exercise-induced signaling on brown adipose tissue, white adipose tissue and skeletal muscle will help on identifying potential molecular therapeutic candidates.

Conditions

Obesity; Diabetes Mellitus; Metabolic Syndrome X

Keywords

BRITE adipose tissue; physical activity; Thermogenesis; Body Temperature Regulation; Energy Metabolism

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in BAT mass and activity evaluated with Positron emission tomography/computed tomography (PET/CT)

  Baseline and 6 month later (immediately after the interventions ends)

Secondary Outcomes (21)

• Change from Baseline in gene expression of white adipose tissue, aliquots will be obtained by biopsies.

  Baseline and 6 month later (immediately after the interventions ends)

• Change from Baseline in gene expression of muscle, aliquots will be obtained by biopsies.

  Baseline and 6 month later (immediately after the interventions ends)

• Change from Baseline in resting energy expenditure measured through indirect calorimetry

  Baseline and 6 month later (immediately after the interventions ends)

• Change from Baseline in meal Induced Thermogenesis measured through indirect calorimetry

  Baseline and 6 month later (immediately after the interventions ends)

• Change from Baseline in Cold Induced Thermogenesis measured through indirect calorimetry

  Baseline and 6 month later (immediately after the interventions ends)

Study Arms (3)

Usual care group (control)

NO INTERVENTION

Participants randomly assigned to the usual care (control) group will receive general advices from the exercise-training specialist about the positive effects of physical activity at the start of the study. The investigators will prepare informative pamphlets describing the benefits of physical activity that the investigators group has prepared for the Region of Andalucía (Southern Spain),http://www.juntadeandalucia.es/salud/servicios/contenidos/andaluciaessalud/docs/130/Guia\_Recomendaciones\_AF.pdf.

Moderate-intensity group

EXPERIMENTAL

Exercise training based on recommendations for adults (WHO)

Other: Exercise training based on recommendations for adults (WHO)

Vigorous-intensity group

EXPERIMENTAL

Exercise training based on recommendations for adults (WHO)

Other: Exercise training based on recommendations for adults (WHO)

Interventions

Exercise training based on recommendations for adults (WHO) OTHER

The length of the trial will be 6 months. the total time of aerobic exercise in both moderate-intensity and vigorous-intensity groups will be 150 minutes/week, whereas the time needed to complete the resistance training exercises will be ≈15-30 minutes for both groups.

Moderate-intensity group; Vigorous-intensity group

Eligibility Criteria

• Age: 18 Years - 25 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI: 20-35 kg/m2.
• Not engaged in regular physical activity \>20 min on \>3 days/week.
• Not participating in a weight loss program.
• Stable weight over the last 3 months (body weight changes \<3 kg).
• Normal electrocardiogram.

You may not qualify if:

• History of cardiovascular disease.
• Diabetes or hypertension.
• Pregnancy, or planning to get pregnant during the study period.
• Medication for hypertension, hyperlipidemia, hyperuricemia or other illness.
• Beta blockers or benzodiazepins use.
• Smoking.
• Frequent exposure to cold temperatures (Granada is surrounded by high mountains where people can sky or do trekking).
• Taking medication for thyroid.
• Other significant medical conditions that are life-threatening or that can interfere with or be aggravated by exercise.
• Unwillingness to either complete the study requirements or to be randomized into control or training group.

Sponsors & Collaborators

• Universidad de Granada: lead
• Instituto de Salud Carlos III: collaborator
• Hospital Clinico Universitario San Cecilio: collaborator
• University Hospital Virgen de las Nieves: collaborator

Study Sites (1)

University of Granada

Granada, Granada, 18011, Spain

RECRUITING

Related Publications (18)

• Martin-Olmedo JJ, Jurado-Fasoli L, Osuna-Prieto FJ, Garcia-Fontana C, Garcia-Fontana B, Gracia-Marco L, Munoz-Torres M, Ruiz JR. Impact of 24-week concurrent training on bone parameters and plasma levels of osteoglycin and sclerostin in young, sedentary adults: secondary analyses from the ACTIBATE randomized controlled trial. Eur J Endocrinol. 2025 Apr 30;192(5):558-567. doi: 10.1093/ejendo/lvaf087.

  PMID: 40298018 DERIVED

• Martinez-Tellez B, Xu H, Ortiz-Alvarez L, Rodriguez-Garcia C, Schonke M, Jurado-Fasoli L, Osuna-Prieto FJ, Alcantara JMA, Acosta FM, Amaro-Gahete FJ, Folkerts G, Vilchez-Vargas R, Link A, Plaza-Diaz J, Gil A, Labayen I, Fernandez-Veledo S, Rensen PCN, Ruiz JR. Effect of a 24-week supervised concurrent exercise intervention on fecal microbiota diversity and composition in young sedentary adults: The ACTIBATE randomized controlled trial. Clin Nutr. 2025 Jun;49:128-137. doi: 10.1016/j.clnu.2025.04.008. Epub 2025 Apr 15.

  PMID: 40279809 DERIVED

• Amaro-Gahete FJ, Espuch-Oliver A, Cano-Nieto A, Alcantara JMA, Garcia-Lario JV, De Haro T, Llamas-Elvira JM, Munoz Torres M, Castillo MJ, Labayen I, Ruiz JR. Impact of 24-week supervised concurrent exercise on S-Klotho and vitamin D levels: A randomized controlled trial. J Sports Sci. 2024 Dec;42(24):2562-2571. doi: 10.1080/02640414.2025.2453328. Epub 2025 Jan 20.

  PMID: 39831661 DERIVED

• Alcantara JMA, Gonzalez-Acedo A, Amaro-Gahete FJ, Plaza-Florido A. Heart Rate and Its Variability Are Associated With Resting Metabolic Rate and Substrate Oxidation in Young Women but Not in Men. Am J Hum Biol. 2024 Nov;36(11):e24157. doi: 10.1002/ajhb.24157. Epub 2024 Sep 20.

  PMID: 39300911 DERIVED

• Dote-Montero M, Acosta FM, Sanchez-Delgado G, Merchan-Ramirez E, Amaro-Gahete FJ, Labayen I, Ruiz JR. Association of meal timing with body composition and cardiometabolic risk factors in young adults. Eur J Nutr. 2023 Aug;62(5):2303-2315. doi: 10.1007/s00394-023-03141-9. Epub 2023 Apr 26.

  PMID: 37100891 DERIVED

• Jurado-Fasoli L, Di X, Sanchez-Delgado G, Yang W, Osuna-Prieto FJ, Ortiz-Alvarez L, Krekels E, Harms AC, Hankemeier T, Schonke M, Aguilera CM, Llamas-Elvira JM, Kohler I, Rensen PCN, Ruiz JR, Martinez-Tellez B. Acute and long-term exercise differently modulate plasma levels of oxylipins, endocannabinoids, and their analogues in young sedentary adults: A sub-study and secondary analyses from the ACTIBATE randomized controlled-trial. EBioMedicine. 2022 Nov;85:104313. doi: 10.1016/j.ebiom.2022.104313. Epub 2022 Oct 27.

  PMID: 36374769 DERIVED

• Ortiz-Alvarez L, Acosta FM, Xu H, Sanchez-Delgado G, Vilchez-Vargas R, Link A, Plaza-Diaz J, Llamas JM, Gil A, Labayen I, Rensen PCN, Ruiz JR, Martinez-Tellez B. Fecal microbiota composition is related to brown adipose tissue 18F-fluorodeoxyglucose uptake in young adults. J Endocrinol Invest. 2023 Mar;46(3):567-576. doi: 10.1007/s40618-022-01936-x. Epub 2022 Oct 15.

  PMID: 36242744 DERIVED

• Martinez-Tellez B, Sanchez-Delgado G, Acosta FM, Alcantara JMA, Amaro-Gahete FJ, Martinez-Avila WD, Merchan-Ramirez E, Munoz-Hernandez V, Osuna-Prieto FJ, Jurado-Fasoli L, Xu H, Ortiz-Alvarez L, Arias-Tellez MJ, Mendez-Gutierrez A, Labayen I, Ortega FB, Schonke M, Rensen PCN, Aguilera CM, Llamas-Elvira JM, Gil A, Ruiz JR. No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial. Nat Commun. 2022 Sep 12;13(1):5259. doi: 10.1038/s41467-022-32502-x.

  PMID: 36097264 DERIVED

• Merchan-Ramirez E, Sanchez-Delgado G, Arrizabalaga-Arriazu C, Acosta FM, Arias-Tellez MJ, Munoz-Torres M, Garcia-Lario JV, Llamas-Elvira JM, Ruiz JR. Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults. J Physiol Biochem. 2022 Aug;78(3):629-640. doi: 10.1007/s13105-022-00881-w. Epub 2022 Apr 6.

  PMID: 35381950 DERIVED

• Mendez-Gutierrez A, Aguilera CM, Osuna-Prieto FJ, Martinez-Tellez B, Rico Prados MC, Acosta FM, Llamas-Elvira JM, Ruiz JR, Sanchez-Delgado G. Exercise-induced changes on exerkines that might influence brown adipose tissue metabolism in young sedentary adults. Eur J Sport Sci. 2023 Apr;23(4):625-636. doi: 10.1080/17461391.2022.2040597. Epub 2022 Apr 25.

  PMID: 35152857 DERIVED

• Acosta FM, Sanchez-Delgado G, Martinez-Tellez B, Alcantara JMA, Llamas-Elvira JM, Ruiz JR. Diurnal variations of cold-induced thermogenesis in young, healthy adults: A randomized crossover trial. Clin Nutr. 2021 Oct;40(10):5311-5321. doi: 10.1016/j.clnu.2021.08.010. Epub 2021 Aug 24.

  PMID: 34536639 DERIVED

• Jurado-Fasoli L, Amaro-Gahete FJ, Merchan-Ramirez E, Labayen I, Ruiz JR. Relationships between diet and basal fat oxidation and maximal fat oxidation during exercise in sedentary adults. Nutr Metab Cardiovasc Dis. 2021 Apr 9;31(4):1087-1101. doi: 10.1016/j.numecd.2020.11.021. Epub 2020 Dec 1.

  PMID: 33549436 DERIVED

• Sanchez-Delgado G, Alcantara JMA, Acosta FM, Martinez-Tellez B, Amaro-Gahete FJ, Merchan-Ramirez E, Lof M, Labayen I, Ravussin E, Ruiz JR. Energy Expenditure and Macronutrient Oxidation in Response to an Individualized Nonshivering Cooling Protocol. Obesity (Silver Spring). 2020 Nov;28(11):2175-2183. doi: 10.1002/oby.22972. Epub 2020 Sep 27.

  PMID: 32985119 DERIVED

• Sanchez-Delgado G, Acosta FM, Martinez-Tellez B, Finlayson G, Gibbons C, Labayen I, Llamas-Elvira JM, Gil A, Blundell JE, Ruiz JR. Brown adipose tissue volume and 18F-fluorodeoxyglucose uptake are not associated with energy intake in young human adults. Am J Clin Nutr. 2020 Feb 1;111(2):329-339. doi: 10.1093/ajcn/nqz300.

  PMID: 31826235 DERIVED

• Acosta FM, Sanchez-Delgado G, Martinez-Tellez B, Migueles JH, Amaro-Gahete FJ, Rensen PCN, Llamas-Elvira JM, Blondin DP, Ruiz JR. Sleep duration and quality are not associated with brown adipose tissue volume or activity-as determined by 18F-FDG uptake, in young, sedentary adults. Sleep. 2019 Dec 24;42(12):zsz177. doi: 10.1093/sleep/zsz177.

  PMID: 31555815 DERIVED

• Amaro-Gahete FJ, Sanchez-Delgado G, Ara I, R Ruiz J. Cardiorespiratory Fitness May Influence Metabolic Inflexibility During Exercise in Obese Persons. J Clin Endocrinol Metab. 2019 Dec 1;104(12):5780-5790. doi: 10.1210/jc.2019-01225.

  PMID: 31322652 DERIVED

• Acosta FM, Martinez-Tellez B, Sanchez-Delgado G, Migueles JH, Contreras-Gomez MA, Martinez-Avila WD, Merchan-Ramirez E, Alcantara JMA, Amaro-Gahete FJ, Llamas-Elvira JM, Ruiz JR. Association of Objectively Measured Physical Activity With Brown Adipose Tissue Volume and Activity in Young Adults. J Clin Endocrinol Metab. 2019 Feb 1;104(2):223-233. doi: 10.1210/jc.2018-01312.

  PMID: 30137350 DERIVED

• Sanchez-Delgado G, Martinez-Tellez B, Olza J, Aguilera CM, Labayen I, Ortega FB, Chillon P, Fernandez-Reguera C, Alcantara JMA, Martinez-Avila WD, Munoz-Hernandez V, Acosta FM, Prados-Ruiz J, Amaro-Gahete FJ, Hidalgo-Garcia L, Rodriguez L, Ruiz YA, Ramirez-Navarro A, Muros-de Fuentes MA, Garcia-Rivero Y, Sanchez-Sanchez R, de Dios Beas Jimenez J, de Teresa C, Navarrete S, Lozano R, Brea-Gomez E, Rubio-Lopez J, Ruiz MR, Cano-Nieto A, Llamas-Elvira JM, Jimenez Rios JA, Gil A, Ruiz JR. Activating brown adipose tissue through exercise (ACTIBATE) in young adults: Rationale, design and methodology. Contemp Clin Trials. 2015 Nov;45(Pt B):416-425. doi: 10.1016/j.cct.2015.11.004. Epub 2015 Nov 3.

  PMID: 26546068 DERIVED

MeSH Terms

Conditions

Obesity; Diabetes Mellitus; Metabolic Syndrome; Motor Activity

Interventions

World Health Organization

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Insulin Resistance; Hyperinsulinism; Behavior

Intervention Hierarchy (Ancestors)

United Nations; International Agencies; Organizations; Health Care Economics and Organizations

Study Officials

• Jonatan R Ruiz, PhD

  Universidad de Granada

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonatan R Ruiz, PhD

CONTACT

+34 958 242 754; ruizj@ugr.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Researcher

Study Record Dates

• First Submitted: February 3, 2015
• First Posted: February 18, 2015
• Study Start: February 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: February 18, 2015

Record last verified: 2015-02

Locations

ES (1)