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.
A tanulmány áttekintése
Állapot
Körülmények
Beavatkozás / kezelés
Részletes leírás
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.
Tanulmány típusa
Beiratkozás (Becsült)
Fázis
- Nem alkalmazható
Kapcsolatok és helyek
Tanulmányi kapcsolat
- Név: Borja Martínez Téllez, PhD
- Telefonszám: +34 950215334
- E-mail: borjammt@ual.es
Tanulmányi helyek
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Almería
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Almería, Almería, Spanyolország, 04131
- Universidad de Almería
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Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
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.
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Alapvető tudomány
- Kiosztás: Véletlenszerűsített
- Beavatkozó modell: Párhuzamos hozzárendelés
- Maszkolás: Egyetlen
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
|
Nincs beavatkozás: Control
n=15; maintaining their usual lifestyle without changes to diet or physical activity; Total 5 days |
|
|
Kísérleti: 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. |
|
Kísérleti: 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. |
|
Kísérleti: 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. |
Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
iBAT adipocyte composition and gene expression (snRNA-seq)
Időkeret: 1 week
|
Change in adipocyte subpopulations and gene expression in dorsocervical iBAT assessed by single-nucleus RNA sequencing (snRNA-seq) |
1 week
|
Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
iBAT mitochondrial respiration (Oroboros O2k).
Időkeret: 1 week
|
Change in mitochondrial respiration in dorsocervical iBAT assessed by high-resolution respirometry. |
1 week
|
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iBAT protein expression (Western blot)
Időkeret: 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
Időkeret: 5 weeks
|
Change in total body fat mass (kg) from baseline, assessed by dual-energy X-ray absorptiometry (DXA). |
5 weeks
|
|
Body Fat Percentage
Időkeret: 5 weeks
|
Change in total body fat percentage (%) from baseline, assessed by dual-energy X-ray absorptiometry (DXA). |
5 weeks
|
|
Resting Metabolic Rate
Időkeret: 5 weeks
|
Change in resting metabolic rate (kcal/day) from baseline, assessed by indirect calorimetry. |
5 weeks
|
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Cardiorespiratory Fitness - Peak Oxygen Uptake (VO₂peak)
Időkeret: 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
Időkeret: 5 weeks
|
Change in fasting LDL cholesterol (mg/dL) from baseline, assessed in blood samples. |
5 weeks
|
|
Urinary Urea Nitrogen
Időkeret: 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
Időkeret: 5 weeks
|
Change in gut microbiota composition assessed in fecal samples. |
5 weeks
|
|
Fat-Free Mass
Időkeret: 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
Időkeret: 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
Időkeret: 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
Időkeret: 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
Időkeret: 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
Időkeret: 5 weeks
|
Change in fasting HDL cholesterol (mg/dL) from baseline, assessed in blood samples. |
5 weeks
|
|
Fasting Glucose
Időkeret: 5 weeks
|
Change in fasting blood glucose (mg/dL) from baseline. |
5 weeks
|
|
Fasting Insulin
Időkeret: 5 weeks
|
Change in fasting insulin concentration (µIU/mL) from baseline, assessed in blood samples. |
5 weeks
|
|
Triglycerides
Időkeret: 5 weeks
|
Change in fasting triglyceride concentration (mg/dL) from baseline, assessed in blood samples. |
5 weeks
|
|
C-Reactive Protein (CRP)
Időkeret: 5 weeks
|
Change in C-reactive protein concentration (mg/L) from baseline, assessed in blood samples. |
5 weeks
|
|
Fat Oxidation During Exercise
Időkeret: 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
Időkeret: 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
|
Együttműködők és nyomozók
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Becsült)
Elsődleges befejezés (Becsült)
A tanulmány befejezése (Becsült)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Tényleges)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
Kulcsszavak
További vonatkozó MeSH feltételek
Egyéb vizsgálati azonosító számok
- PID2025-173649OB-I00
Terv az egyéni résztvevői adatokhoz (IPD)
Tervezi megosztani az egyéni résztvevői adatokat (IPD)?
IPD megosztási időkeret
5 years after publishing the data
IPD-megosztási hozzáférési feltételek
Everybody
Az IPD megosztását támogató információ típusa
- STUDY_PROTOCOL
- ICF
- CSR
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