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ACTIBATE Activating brown adipose tissue through exercise in young adults: A Randomized controlled trial

IP: Jonatan R Ruiz
Contacto: ruizj@ugr.es

Summary

The energy expenditure capacity of brown adipose tissue (BAT) makes it an attractive target as a therapy against obesity and type 2 diabetes. BAT activators namely catecholamines, natriuretic peptides and certain myokines, are secreted in response to exercise.
ACTIBATE will determine the effect of exercise on BAT activity and mass measured by positron emission tomography/computed tomography (PET/CT, primary outcome) in young adults. ACTIBATE will also investigate the physiological consequences of activating BAT (secondary outcomes).
ACTIBATE will recruit 150 sedentary, healthy, young adults (50% women) aged 18–25 years. Eligible participants will be randomly assigned to a non-exercise group (n≈50) or one of two exercise groups (n=50 each). Participants in the exercise groups will perform aerobic and strength training 3–4 days/week at a heart rate equivalent to 60% of heart rate reserve (HRres), and at 50% of 1 repetition maximum (RM) for the moderate-intensity group, and at 80% of HRres and 70%RMfor the vigorous-intensity group. Laboratory measures completed at baseline and 6 months include BAT activity and mass, resting energy expenditure, meal and cold-induced thermogenesis, body temperature regulation and shivering threshold, body composition and cardiovascular disease risk factors. We will also obtain biopsies from abdominal subcutaneous white adipose tissue and skeletal muscle to analyse the expression of genes encoding proteins involved in the thermogenic machinery.
ClinicalTrials.gov ID:NCT02365129

Status

  • Exercise intervention and data collection finished.
  • The main articles of this study are already published, yet some others are under preparation.

Funding

The study is supported by the Spanish Ministry of Economy and Competitiveness, Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), Fondos Europeo de Desarrollo Regional (FEDER), by the Spanish Ministry of Science and Innovation (RYC-2010-05957, RYC-2011-09011), by the Spanish Ministry of Education (FPU 13/04365, FPU15/04059, y Beca de Colaboración Ref. 11727189), by the University of Granada (Beca de Iniciación a la Investigación), by the Fundación Iberoamericana de Nutrición (FINUT), by the Redestemáticas de investigación cooperativa RETIC (Red SAMID RD12/0026/0015), by AstraZeneca HealthCare Foundation, and by Vegenat®.

Selected Publications

Study protocol and article reporting the primary outcome:

  • Sanchez-Delgado G, Martinez-Tellez B, Olza J, Aguilera CM, Labayen I, Ortega FB, Chillon P, Fernandez-Reguera C, Alcantara JM, Martinez-Avila WD, Muñoz-Hernandez V, Acosta FM, Prados-Ruiz J, Amaro-Gahete FJ, Hidalgo-Garcia L, Rodriguez L, Ruiz YA, Ramirez-Navarro A, Muros-de Fuentes MA, García-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):416-25. DOI: https://doi.org/10.1016/j.cct.2015.11.004
  • Martinez-Tellez B, Sanchez-Delgado G, Acosta FM, Alcantara JMA, Amaro-Gahete FJ, Martinez-Avila WD, Merchan-Ramirez E, Muñoz-Hernandez V, Osuna-Prieto FJ, Jurado-Fasoli L, Xu H, Ortiz-Alvarez L, Arias-Tellez MJ, Mendez-Gutierrez A, Labayen I, Ortega FB, Schönke M, Rensen PCN, Aguilera CM, Llamas-Elvira JM, Gil Á, 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: https://doi.org/10.1038/s41467-022-32502-x

Other articles derived from the ACTIBATE project:

  1. Jurado-Fasoli L, Sanchez-Delgado G, Di X, Yang W, Kohler I, Villarroya F, Aguilera CM, Hankemeier T, Ruiz JR, Martinez-Tellez B. Cold-induced changes in plasma signaling lipids are associated with a healthier cardiometabolic profile independently of brown adipose tissue. Cell Rep Med. 2024 Feb 20;5(2):101387. DOI: https://doi.org/10.1016/j.xcrm.2023.101387
  2. Jurado-Fasoli L, Sanchez-Delgado G, Alcantara JMA, Acosta FM, Sanchez-Sanchez R, Labayen I, Ortega FB, Martinez-Tellez B, Ruiz JR. Adults with metabolically healthy overweight or obesity present more brown adipose tissue and higher thermogenesis than their metabolically unhealthy counterparts. EBioMedicine. 2024 Feb;100:104948. DOI: https://doi.org/10.1016/j.ebiom.2023.104948
  3. Camacho-Cardenosa A, Amaro-Gahete FJ, Martinez-Tellez B, Alcantara JMA, Ortega FB, Ruiz JR. Sex-specific dose-response effects of a 24-week supervised concurrent exercise intervention on cardiorespiratory fitness and muscular strength in young adults: The ACTIBATE randomized controlled trial.Scand J Med Sci Sports. 2024 Jan;34(1):e14507. DOI: https://doi.org/10.1111/sms.14507
  4. Amaro-Gahete FJ, Ruiz-Ruiz M, Cano-Nieto A, Sanchez-Delgado G, Alcantara JMA, Acosta FM, Labayen I, Ortega FB, Ruiz JR. Effect of Moderate Versus Vigorous Exercise Intensity on Body Composition in Young Untrained Adults: The Activating Brown Adipose Tissue Through Exercise (ACTIBATE) Randomized Controlled Trial. Int J Sport Nutr Exerc Metab. 2023 Sep 21;33(6):331-341. DOI: https://doi.org/10.1123/ijsnem.2023-0085
  5. Jurado-Fasoli L, Di X, Sanchez-Delgado G, Yang W, Osuna-Prieto FJ, Ortiz-Alvarez L, Krekels E, Harms AC, Hankemeier T, Schönke 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: https://doi.org/10.1016/j.ebiom.2022.104313
  6. Sanchez-Delgado G, Martinez-Tellez B, Acosta FM, Virtue S, Vidal-Puig A, Gil A, Llamas-Elvira JM, Ruiz JR. Brown Adipose Tissue Volume and Fat Content Are Positively Associated With Whole-Body Adiposity in Young Men-Not in Women. Diabetes. 2021 Jul;70(7):1473-1485. https://doi.org/10.2337/db21-0011
  7. Sanchez-Delgado G, Acosta FM, Martinez-Tellez B, Finlayson G, Gibbons C, Labayen I, Llamas-Elvira JM, Gil A, Blundell JE, Ruiz JR. Am J Clin Nutr. 2020 Feb 1;111(2):329-339. DOI: https://doi.org/10.1093/ajcn/nqz300
  8. Martinez-Tellez B, Sanchez-Delgado G, Alcantara JMA, Acosta FM, Amaro-Gahete FJ, Osuna-Prieto FJ, Perez-Bey A, Jimenez-Pavon D, Llamas-Elvira JM, Gil A, Aguilera CM, Rensen PCN, Ruiz JR. Evidence of high 18 F-fluorodeoxyglucose uptake in the subcutaneous adipose tissue of the dorsocervical area in young adults. Exp Physiol. 2019 Feb;104(2):168-173. DOI: https://doi.org/10.1113/ep087428

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