Clinical trial NCT05884177: Inuit and Cold Exposure
Official title: Metabolic Effects of Short-term Cold Exposure Among Greenlanders and Non-Greenlanders
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Healthy
Keywords: Brown Adipose Tissue
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: Greenland University
First posted: 2023-06-01
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy, lean, young Greenlanders and non-Greenlanders living in Denmark

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: BAT detection
timeFrame: Through study completion, analysis for an average of 1 year
Secondary outcomes:
measure: Temperature of the core and at the skin on multiple sites
timeFrame: Through study completion, analysis for an average of 1 year
measure: Changes in thyroid function
timeFrame: Through study completion, analysis for an average of 1 year
measure: Changes in metabolites
timeFrame: Through study completion, analysis for an average of 1 year
measure: Insulin sensitivity
timeFrame: Through study completion, analysis for an average of 1 year
measure: Adipose tissue composition
timeFrame: Through study completion, analysis for an average of 1 year
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
Study officials:
References: