Intermittent Cold Exposure and Brown Adipose Tissue Hyperplasia

Investigating the Cellular Heterogeneity of Human Brown Adipose Tissue and Its (Patho)Physiological Regulation

This clinical trial explores how repeated short-term cold exposure impacts the molecular and physiological function of brown adipose tissue (BAT), a thermogenic organ associated with improved cardiometabolic health. While intermittent cold exposure has been shown to increase BAT activity and mass, as measured by fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography/computed tomography (PET/CT) scans, the molecular adaptations within BAT and other thermogenic tissues including skeletal muscle and white adipose tissue (WAT) remain poorly understood.

Healthy adults aged 18 to 40 years (6 males and 6 females) will participate in a 10-day cold acclimation protocol (2 hours per day using water-perfused cooling blankets). The primary objective is to determine how cold exposure alters cellular heterogeneity and gene expression in BAT, WAT, and skeletal muscle.

Participants will undergo baseline assessments, including measurements of energy expenditure, core and skin temperature, muscle activity, and blood sampling, each performed in both warm and cold conditions. These assessments will be followed by dynamic total-body PET/CT imaging during cold exposure and tissue biopsies from BAT, subcutaneous WAT, and skeletal muscle. These procedures will be repeated after the cold acclimation protocol to evaluate physiological and molecular changes. Additional outcomes include changes in energy expenditure, cold tolerance, and immune cell responses induced by cold exposure.

Twelve healthy adults aged 18-40 years old (6 female, 6 male) will:

• Attend baseline visits in both warm and cold conditions for blood sampling, measurement of energy expenditure, skin and core temperature, muscle activity. This will be followed by dynamic total-body 18F-FDG PET/CT scan during cold exposure.
• Undergo biopsies of BAT (supraclavicular), skeletal muscle (vastus lateralis), and subcutaneous WAT (periumbilical) under local anesthesia.
• Complete 10 consecutive days of cold acclimation (2 hours per day) using water-perfused cooling blankets.
• Return for follow-up assessments, including repeat blood sampling, energy expenditure, temperature measurements, PET/CT imaging, and tissue biopsies to evaluate post-acclimation changes.

Inclusion Criteria:

• Aged 18-40 years
• Body mass index 18.5-25 kg/m2
• Weight change of less than 5% in the past 6 months
• No acute or chronic medical conditions
• On no regular medications (other than contraceptives in female participants)
• No claustrophobia
• Alcohol intake ≤14 units/ week
• Screening blood tests within acceptable limits (of no clinical significance)
• Not currently pregnant, lactating or breastfeeding (female participants only)
• Ability to provide informed consent.

Exclusion Criteria:

• Not meeting inclusion criteria
• Contra-indication to PET/CT scan
• Allergy to local anaesthetic