Exercise and Prolonged Fasting to Improve Brown Adipose Tissue Function in Postmenopausal Women (EMPOWER-BAT)
Exercise and Prolonged Fasting to Improve Interscapular Brown Fat Mitochondrial Function and Enhance Metabolic Flexibility in Postmenopausal Women (EMPOWER-BAT)
Type of Study: Clinical Trial
Goal: The goal of this clinical trial is to investigate mitochondrial function in interscapular brown adipose tissue (iBAT) in postmenopausal women and determine whether aerobic exercise, prolonged fasting, or their combination can improve iBAT mitochondrial function and whole-body metabolic flexibility.
Participant Population/Health Conditions: The study will involve 60 postmenopausal women aged 45-65 years living with overweight or obesity.
Main Questions: The main questions this study aims to answer are:
- What are the mitochondrial function and cellular characteristics of iBAT in postmenopausal women?
- Can aerobic exercise or five-day prolonged fasting improve mitochondrial function in iBAT and whole-body metabolic flexibility?
- Does combining aerobic exercise with prolonged fasting produce greater metabolic adaptations than either intervention alone?
- Are improvements in metabolic flexibility maintained four weeks after the intervention?
Participants Will:
Be randomized into one of four groups: control, aerobic exercise, prolonged fasting, or combined aerobic exercise plus prolonged fasting.
Follow their assigned intervention for five consecutive days. Undergo metabolic and physiological assessments before and after the intervention and again four weeks later.
Provide dorsocervical adipose tissue biopsies and biological samples to investigate mitochondrial function, adipocyte characteristics, and metabolic adaptations.
Comparison Group: Researchers will compare the effects of aerobic exercise, prolonged fasting, and their combination with a control condition to determine their effects on iBAT mitochondrial function and whole-body metabolic flexibility.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Postmenopause is associated with a substantial increase in cardiometabolic risk, partly driven by the decline in estrogen levels and alterations in cellular energy metabolism. Mitochondrial dysfunction has been documented in skeletal muscle of postmenopausal women and is associated with metabolic inflexibility, reduced fat oxidation, ectopic fat accumulation, and insulin resistance. However, whether mitochondrial dysfunction is also present in adipose tissue of postmenopausal women, and whether it can be reversed through lifestyle interventions, remains largely unknown.
Brown adipose tissue (BAT) is a mitochondria-rich and metabolically active tissue involved in thermogenesis and substrate utilization. Although human BAT has traditionally been studied in the supraclavicular region, emerging evidence from our research group suggests the presence of a metabolically active adipose tissue depot in the dorsocervical region, referred to as interscapular brown adipose tissue (iBAT). Preliminary observations indicate that this depot may have distinct metabolic characteristics. However, iBAT has not yet been characterized in postmenopausal women.
Aerobic exercise is a potent non-pharmacological stimulus for mitochondrial remodeling and improves mitochondrial biogenesis and oxidative capacity. Exercise-derived lactate may also promote adipose tissue browning and mitochondrial remodeling. Prolonged fasting induces profound metabolic adaptations characterized by increased fat mobilization and changes in substrate utilization. Preliminary data from our group suggest that five days of prolonged fasting substantially increase fat oxidation during exercise, providing a rationale for investigating whether fasting and exercise may have complementary effects on mitochondrial function and metabolic flexibility.
Based on this rationale, the main hypothesis of EMPOWER-BAT is that iBAT in postmenopausal women presents mitochondrial dysfunction and that aerobic exercise, five-day prolonged fasting, and their combination can improve mitochondrial function through lactate-related signaling pathways, leading to enhanced whole-body metabolic flexibility. The main objective is to characterize mitochondrial function in iBAT and determine the effects of these interventions on iBAT mitochondrial function and metabolic flexibility.
EMPOWER-BAT is a randomized controlled trial involving 60 postmenopausal women aged 45-65 years with a body mass index ≥25 kg/m². Participants will be randomized (1:1:1:1) into four groups: a control group maintaining its usual lifestyle; an aerobic exercise group performing supervised exercise for 60-90 minutes at 65% of heart rate reserve; a prolonged fasting group following a medically supervised fasting protocol providing approximately 600 kcal/day; or a combined group completing both exercise and fasting. All interventions will last five consecutive days.
Before and after the intervention, iBAT biopsies will be collected from the dorsocervical region to assess mitochondrial function and adipocyte characteristics. Metabolic and physiological assessments will include indirect calorimetry at rest and during exercise, body composition, cardiorespiratory fitness, and blood and urine biomarkers. Continuous glucose and ketone monitoring will also be performed during the intervention. Four weeks later, metabolic and physiological assessments will be repeated to determine whether changes in metabolic flexibility are maintained after participants return to their usual lifestyle.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Borja Martínez Téllez, PhD
- Número de teléfono: +34 950215334
- Correo electrónico: borjammt@ual.es
Ubicaciones de estudio
-
-
Almería
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Almería, Almería, España, 04131
- Universidad de Almería
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-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Women aged 45 to 65 years.
- Postmenopausal status, defined as ≥ 12 consecutive months without menstruation.
- Women with amenorrhea shorter than 12 months will be included if their follicle-stimulating hormone levels are >30IU/liter.
- BMI between ≥25 kg/m2.
- Sedentary or low-active (not meeting physical activity guidelines).
- Willing to be randomized to any of the four groups.
- Able and willing to adhere to all study procedures and show availabity in their schedule.
- Must be willing to have biological samples stored for future research.
Exclusion Criteria:
- Diabetes mellitus (determined based on fasting glucose levels defined by ADA criteria).
- Any other active endocrine disease (thyroid disease, any signs of Cushing's syndrome, adrenal disease and lipid-associated disorders such as familial hypercholesterolemia).
- Any cardiac disease (i.e., ischemic cardiac disease, arrhythmias, severe heart failure).
- Use of medication known to influence glucose and/or lipid metabolism or brown fat activity (e.g., beta-blockers, antidepressants, corticosteroids).
- Current or recent (past 6 months) use of hormone replacement therapy, including systemic estrogen therapy (oral or transdermal), combined estrogen-progestin therapy, tibolone, or selective estrogen receptor modulators.
- Clinically relevant abnormalities in clinical chemistry or electrocardiogram at screening (to be judged by the study physician).
- A first-degree family member with sudden cardiac death.
- Any chronic renal or hepatic disease.
- Abuse of alcohol or other substances.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Sin intervención: Control
n=15; maintaining their usual lifestyle without changes to diet or physical activity; Total 5 days |
|
|
Experimental: Aerobic exercise
n=15; receiving supervised aerobic exercise for 60-90 minutes/day at 65% of heart rate reserve; Total 5 days |
Participants will perform supervised aerobic exercise for 60-90 minutes per day at 65% of heart rate reserve on 5 consecutive days. |
|
Experimental: Prolonged fasting
n=15; following a prolonged fasting protocol providing approximately 600 kcal/day; Total 5 days |
Participants will follow a medically supervised prolonged fasting protocol providing approximately 600 kcal/day for five consecutive days. |
|
Experimental: Aerobic exercise + prolonged fasting
n=15; receiving supervised aerobic exercise for 60-90 minutes/day at 65% of heart rate reserve and prolonged fasting providing approximately 600 kcal/day; Total 5 days |
Participants will perform supervised aerobic exercise for 60-90 minutes per day at 65% of heart rate reserve on 5 consecutive days. Participants will follow a medically supervised prolonged fasting protocol providing approximately 600 kcal/day for five consecutive days. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
iBAT adipocyte composition and gene expression (snRNA-seq)
Periodo de tiempo: 1 week
|
Change in adipocyte subpopulations and gene expression in dorsocervical iBAT assessed by single-nucleus RNA sequencing (snRNA-seq) |
1 week
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
iBAT mitochondrial respiration (Oroboros O2k).
Periodo de tiempo: 1 week
|
Change in mitochondrial respiration in dorsocervical iBAT assessed by high-resolution respirometry. |
1 week
|
|
iBAT protein expression (Western blot)
Periodo de tiempo: 1 week
|
Change in protein expression in dorsocervical iBAT assessed by Western blot, including markers related to thermogenesis and mitochondrial function. |
1 week
|
|
Total Body Fat Mass
Periodo de tiempo: 5 weeks
|
Change in total body fat mass (kg) from baseline, assessed by dual-energy X-ray absorptiometry (DXA). |
5 weeks
|
|
Body Fat Percentage
Periodo de tiempo: 5 weeks
|
Change in total body fat percentage (%) from baseline, assessed by dual-energy X-ray absorptiometry (DXA). |
5 weeks
|
|
Resting Metabolic Rate
Periodo de tiempo: 5 weeks
|
Change in resting metabolic rate (kcal/day) from baseline, assessed by indirect calorimetry. |
5 weeks
|
|
Cardiorespiratory Fitness - Peak Oxygen Uptake (VO₂peak)
Periodo de tiempo: 5 weeks
|
Change from baseline in peak oxygen uptake (VO₂peak; mL/kg/min), assessed during exercise testing with breath-by-breath gas exchange analysis. |
5 weeks
|
|
LDL Cholesterol
Periodo de tiempo: 5 weeks
|
Change in fasting LDL cholesterol (mg/dL) from baseline, assessed in blood samples. |
5 weeks
|
|
Urinary Urea Nitrogen
Periodo de tiempo: 5 weeks
|
Change from baseline in urinary urea nitrogen (UUN) concentration (mg/dL), assessed in urine samples as a marker of protein metabolism. |
5 weeks
|
|
Gut microbiota
Periodo de tiempo: 5 weeks
|
Change in gut microbiota composition assessed in fecal samples. |
5 weeks
|
|
Fat-Free Mass
Periodo de tiempo: 5 weeks
|
Change in total fat-free mass (kg) from baseline, assessed by dual-energy X-ray absorptiometry (DXA). |
5 weeks
|
|
Visceral Adipose Tissue (VAT) Fat Mass
Periodo de tiempo: 5 weeks
|
Change in visceral adipose tissue (VAT) fat mass (g) from baseline, assessed by dual-energy X-ray absorptiometry (DXA). |
5 weeks
|
|
Subcutaneous Adipose Tissue (SAT) Fat Mass
Periodo de tiempo: 5 weeks
|
Change in subcutaneous adipose tissue (SAT) fat mass (g) from baseline, assessed by dual-energy X-ray absorptiometry (DXA). |
5 weeks
|
|
Fat Oxidation Rate at Rest
Periodo de tiempo: 5 weeks
|
Change in resting fat oxidation rate (g/min) from baseline, calculated from oxygen consumption (VO₂) and carbon dioxide production (VCO₂) measured by indirect calorimetry. |
5 weeks
|
|
Carbohydrate Oxidation Rate at Rest
Periodo de tiempo: 5 weeks
|
Change in resting carbohydrate oxidation rate (g/min) from baseline, calculated from oxygen consumption (VO₂) and carbon dioxide production (VCO₂) measured by indirect calorimetry. |
5 weeks
|
|
HDL Cholesterol
Periodo de tiempo: 5 weeks
|
Change in fasting HDL cholesterol (mg/dL) from baseline, assessed in blood samples. |
5 weeks
|
|
Fasting Glucose
Periodo de tiempo: 5 weeks
|
Change in fasting blood glucose (mg/dL) from baseline. |
5 weeks
|
|
Fasting Insulin
Periodo de tiempo: 5 weeks
|
Change in fasting insulin concentration (µIU/mL) from baseline, assessed in blood samples. |
5 weeks
|
|
Triglycerides
Periodo de tiempo: 5 weeks
|
Change in fasting triglyceride concentration (mg/dL) from baseline, assessed in blood samples. |
5 weeks
|
|
C-Reactive Protein (CRP)
Periodo de tiempo: 5 weeks
|
Change in C-reactive protein concentration (mg/L) from baseline, assessed in blood samples. |
5 weeks
|
|
Fat Oxidation During Exercise
Periodo de tiempo: 5 weeks
|
Change from baseline in fat oxidation rate (g/min) during exercise, estimated by indirect calorimetry using a COSMED Quark metabolic cart. |
5 weeks
|
|
Carbohydrate Oxidation During Exercise
Periodo de tiempo: 5 weeks
|
Change from baseline in carbohydrate oxidation rate (g/min) during exercise, estimated by indirect calorimetry using a COSMED Quark metabolic cart. |
5 weeks
|
Colaboradores e Investigadores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- PID2025-173649OB-I00
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Marco de tiempo para compartir IPD
5 years after publishing the data
Criterios de acceso compartido de IPD
Everybody
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- CIF
- RSC
Información sobre medicamentos y dispositivos, documentos del estudio
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