Exercise and Prolonged Fasting to Improve Interscapular Brown Fat Mitochondrial Function and Enhance Metabolic Flexibility in Postmenopausal Women (EMPOWER-BAT)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Universidad de Almeria
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- iBAT adipocyte composition and gene expression (snRNA-seq)
Study Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Single (Investigator)
Eligibility Criteria
- Ages
- 45 Years to 65 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
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/m
- •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.
Arms & Interventions
Control
n=15; maintaining their usual lifestyle without changes to diet or physical activity; Total 5 days
Prolonged fasting
n=15; following a prolonged fasting protocol providing approximately 600 kcal/day; Total 5 days
Intervention: Prolonged fasting (Behavioral)
Aerobic exercise
n=15; receiving supervised aerobic exercise for 60-90 minutes/day at 65% of heart rate reserve; Total 5 days
Intervention: Aerobic exercise (Behavioral)
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
Intervention: Aerobic exercise (Behavioral)
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
Intervention: Prolonged fasting (Behavioral)
Outcomes
Primary Outcomes
iBAT adipocyte composition and gene expression (snRNA-seq)
Time Frame: 1 week
Change in adipocyte subpopulations and gene expression in dorsocervical iBAT assessed by single-nucleus RNA sequencing (snRNA-seq)
Secondary Outcomes
- iBAT mitochondrial respiration (Oroboros O2k).(1 week)
- iBAT protein expression (Western blot)(1 week)
- Total Body Fat Mass(5 weeks)
- Body Fat Percentage(5 weeks)
- Resting Metabolic Rate(5 weeks)
- Cardiorespiratory Fitness - Peak Oxygen Uptake (VO₂peak)(5 weeks)
- LDL Cholesterol(5 weeks)
- Urinary Urea Nitrogen(5 weeks)
- Gut microbiota(5 weeks)
- Fat-Free Mass(5 weeks)
- Fasting Glucose(5 weeks)
- Visceral Adipose Tissue (VAT) Fat Mass(5 weeks)
- Subcutaneous Adipose Tissue (SAT) Fat Mass(5 weeks)
- Fat Oxidation Rate at Rest(5 weeks)
- Carbohydrate Oxidation Rate at Rest(5 weeks)
- HDL Cholesterol(5 weeks)
- Fasting Insulin(5 weeks)
- Triglycerides(5 weeks)
- C-Reactive Protein (CRP)(5 weeks)
- Fat Oxidation During Exercise(5 weeks)
- Carbohydrate Oxidation During Exercise(5 weeks)
Investigators
Borja Martínez Tellez
Principal Investigator
Universidad de Almeria