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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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ACTIBATE Activating Brown Adipose Tissue through Exercise

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

Resumen

La capacidad del tejido adiposo pardo (TAP) para incrementar el metabolismo basal le convierte en un tejido diana para las terapias anti-obesidad y diabetes. El sistema nervioso simpático es principal regulador de la actividad del TAP; sin embargo, resultados recientes han puesto de manifiesto la existencia de un conjunto de activadores del TAP que parecen no necesitar la regulación del sistema nervioso simpático. De interés es que estos activadores son sensibles al ejercicio, lo que abre nuevas oportunidades para estudiar el efecto terapéutico del ejercicio. Además, se ha descubierto recientemente una nueva proteína que se libera en el músculo, la irisina, que parece jugar un papel muy importante en el programa de transformación del tejido adiposo blanco a TAP (marronamiento, del inglés browning program). Es de sumo interés clínico y de salud pública determinar si un programa de ejercicio es capaz de incrementar la actividad y cantidad de TAP a través de la estimulación de precursores de este tejido así como de activar la transformación de tejido adiposo blanco en TAP en humanos. Por lo tanto, el objetivo principal del presente estudio aleatorizado controlado es analizar el efecto de un programa de ejercicio de 24 semanas de duración sobre la actividad y cantidad de TAP (primary outcome) en adultos jóvenes. Además, se estudiarán los efectos del ejercicio a nivel molecular en el tejido adiposo blanco y tejido muscular (secondary outcomes).
ClinicalTrials.gov ID:NCT02365129

Estado

  • Intervención y recogida de datos finalizada.
  • Los artículos principales del estudio están ya publicados y algunos estudios adicionales están actualmente en preparación.

Financiación

Este estudio está financiado por el Ministerio de Economía y Competitividad, Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), Fondos Europeo de Desarrollo Regional (FEDER), por el Ministerio de Educación (FPU 13/04365, FPU15/04059, y Beca de Colaboración Ref. 11727189), por la Universidad de Granada (Beca de Iniciación a la Investigación), por la Fundación Iberoamericana de Nutrición (FINUT), por las Redes temáticas de investigación cooperativa RETIC (Red SAMID RD12/0026/0015), por AstraZeneca HealthCare Foundation y por Vegenat®.

Publicaciones seleccionadas

Artículo metodológico y artículo principal del estudio:

  • 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

Otros artículos derivados del proyecto ACTIBATE:

  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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