Intermittent Cold Exposure and Brown Adipose Tissue Hyperplasia

Summary

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.

Conditions

• Brown Adipose Tissue
• Cold Exposure
• 18F-FDG PET/CT

Interventions

OTHER

Cooling

Participants will undergo cold exposure during the baseline and final visits (2.5 hours each visit), as well as throughout the 10-day cold acclimation period (2 hours per day). This will be achieved using water-perfused blankets set to individualized temperatures, selected to elicit comparable physiological responses across participants.

PROCEDURE

Biopsies

Under local anesthesia, biopsies will be obtained from the following sites: * Brown adipose tissue from the supraclavicular (collarbone) region, guided by computed tomography (CT). * White adipose tissue from the abdominal (periumbilical) area. * Skeletal muscle from the outer thigh, specifically the vastus lateralis. These biopsies will be performed both before and after the 10-day cold acclimation protocol.

RADIATION

Injection of 18F-FDG

Intravenous injection of 18F-FDG will be performed after 2 hours of cold exposure. This will be followed by a 30min dynamic total PET/CT scan while cold exposed using water-perfused blankets. These procedures will take place before and after the 10 day-cold acclimation protocol.

OTHER

Indirect calorimetry

Participants will rest quietly while oxygen consumption and carbon dioxide production are continuously recorded using a indirect calorimeter. These data will be used to calculate energy expenditure and respiratory exchange ratio. This procedure will take place before and after the 10 day-cold acclimation protocol.

OTHER

Electromyogram

Skin surface electrodes will be placed on major skeletal muscles to measure shivering and muscle activity during both warm and cold conditions. This procedure will take place before and after the 10 day-cold acclimation protocol.

OTHER

Core and skin temperature monitoring

Participants will ingest an electronic capsule that wirelessly and continuously monitors core body temperature. This procedure will be conducted before and after the 10-day cold acclimation protocol. Additionally, wireless temperature sensors will placed at multiple standardized sites on the body to measure skin temperature. This procedure will be performed before, during, and after the 10-day cold acclimation protocol.

Sponsors & Collaborators

• University of Edinburgh

  lead OTHER

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-05-01

Primary Completion

2026-07-31

Completion

2026-07-31

Countries

• United Kingdom

Study Locations