Inuit and Cold Exposure (ICE)
Metabolic Effects of Short-term Cold Exposure Among Greenlanders and Non-Greenlanders
Brown adipose tissue (BAT) produces heat through non-shivering thermogenesis. It is activated by cold exposure, and when activated it utilizes fatty acids and glucose in order to produce heat. The tissue is especially present in newborns, who not yet have gained a layer of insulating fat to protect from heat loss, and not yet have gained much muscle to produce heat through shivering thermogenesis.
It was long thought that BAT mass hereafter would retract. Modern imaging tools have proved that BAT is persistent and active in some adults. The presence and activity of BAT is negatively correlated with obesity and obesity-related metabolic disorders. The tissue retracts with advancing age and increasing BMI, and it is sensitive to environmental factors, such as diet, weather and climate. The key to activating BAT in subjects that have lost it remains elusive.
BAT is activated to produce heat when exposed to cold. Populations that are most cold exposed include people living in the Arctic. It is known that people of Arctic origin such as indigenous Inuit and indigenous Siberians have genetically adapted to and are acclimatized to the cold through several genetic changes, and possibly by upregulating BAT depots and activity. The investigators aim to dig deeper into the activation mechanisms in BAT, by investigating BAT mass and activity in Greenlanders and non-Greenlanders by use of stage-of-the-art modern techniques.
Study Overview
Detailed Description
Several studies have examined the function of brown adipose tissue (BAT), which is an important source of non-shivering thermogenesis. It has gained attention as a potential target for combating obesity.
BAT has a distinct influence on glucose and triglyceride clearance, and insulin sensitivity, and it has a negative correlation with cardiometabolic risk markers.
BAT activity is correlated with cold temperatures. Observational studies in Greenland are consistent with raised consumption of thyroid hormone and higher thyroid hormone turnover in cold-exposed Inuit compared to Inuit with some and limited cold exposure.
However, these are indirect data that merely suggest the presence of BAT. The presence of active BAT directly illustrated by using an individualized cooling protocol and FDG-PET/CT-scan raises interest in the origin and characterization of intermediate adipose cells (beige adipose tissue) from the white adipose tissue.
Based on the strong correlation between BAT and cardiometabolic health and the evolutionary pressure on Inuit to handle cold environments, the investigators will measure the cold-induced BAT activity and white fat differentiation and assess a connection with genetic and physiological characteristics ot add insight into the biology and regulation of BAT in relation to fat depots in humans.
Participants of Danish and Greenlandic origin will be included for a focus on visualizing brown adipose tissue by use of PET/CT-scans before and after short term cold exposure. Additional sampling includes subcutaneous fat biopsies, blood samples, blood pressure, pulse, temperature of the skin and core, and IRT.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Mette MM Jensen, MD
- Phone Number: +4597660000
- Email: mette.malene@rn.dk
Study Contact Backup
- Name: Stig Andersen, MD, PhD
- Phone Number: +4597660000
- Email: lasa@rn.dk
Study Locations
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-
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Aalborg, Denmark, 9000
- Recruiting
- Aalborg University Hospital
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Contact:
- Mette MM Jensen, MD
- Phone Number: +4597660000
- Email: mette.malene@rn.dk
-
Contact:
- Stig Andersen, MD, PhD
- Phone Number: +4597660000
- Email: lasa@rn.dk
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Ability to give informed consent
- Ability to follow written and verbal instructions
Exclusion Criteria:
- Pregnancy and breastfeeding
- Alpha- or beta-adrenergic affecting medication.
- Thyroid dysfunction
- Liver or kidney disease
- Treatment for diabetes
- MODY and TBC1D4
- Treatment of obesity
- Cardiovascular disease
- Cancer within 3 years
- Mb Renaud
- Hospitalisation for psychiatric disease
- Antipsychotic medication
- Drug abuse within 1-year
- Alcohol abuse
- Plasma glucose > 11 mM
- BMI >35 kg/m2
- Winter swimmer
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Greenlanders
Subjects born in Greenland with parents born in Greenland
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Short-term cold exposure
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non-Greenlanders
Subjects not born in Greenland with parents not born in Greenland
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Short-term cold exposure
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
BAT detection
Time Frame: Through study completion, analysis for an average of 1 year
|
BAT mass in the cervical-upper thoracic, abdominal, and paravertebral regions at room temperature and following short-term cold exposure.
BAT mass on PET/CT scans will be quantified by the degree of glucose uptake: Maximum standard unit value (SUVmax)
|
Through study completion, analysis for an average of 1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Temperature of the core and at the skin on multiple sites
Time Frame: Through study completion, analysis for an average of 1 year
|
Temperature of the core and at the skin on multiple sites.
Core temperature measured with rectal thermometer.
Skin temperatures measured with skin thermometer probes and infrared thermography (IRT).
|
Through study completion, analysis for an average of 1 year
|
|
Changes in thyroid function
Time Frame: Through study completion, analysis for an average of 1 year
|
Changes in thyroid function as measured by plasma TT3, TT4 and TSH
|
Through study completion, analysis for an average of 1 year
|
|
Changes in metabolites
Time Frame: Through study completion, analysis for an average of 1 year
|
Changes in metabolites: Plasma glucose, acylcarnitine and triglycerides
|
Through study completion, analysis for an average of 1 year
|
|
Insulin sensitivity
Time Frame: Through study completion, analysis for an average of 1 year
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Insulin sensitivity
|
Through study completion, analysis for an average of 1 year
|
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Adipose tissue composition
Time Frame: Through study completion, analysis for an average of 1 year
|
Subcutaneous fat biopsies will be examined in relation to white adipose tissue (WAT) function and presence of beige adipocytes
|
Through study completion, analysis for an average of 1 year
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- F2023-040
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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