Vitamin A in Brown Fat Activity

Study Overview
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Brief Summary
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Vitamin A metabolites (retinoids) have shown to activate brown fat function in preclinical studies, however the role of retinoids in human brown fat physiology and energy metabolism remains elusive. This study aims to identify a possible association between retinoid metabolism, brown fat activity, and energy expenditure in lean and obese subjects by using FDG-PET-CT, PET-MR Scans and indirect calorimetry. Additionally we will analyze the genetic profile of white and brown neck fat biopsies at room temperature and cold conditions in a subset of the study participants. More detailed molecular studies (involving other potential browning markers) will also be performed in adipocytes derived from human SVC. The optimal duration of cold exposure will be determined in a pilot study. Therefore subjects will be repeatedly exposed to cold and circulating retinoid levels and other plasma parameters will be measured at various time points.

Official Title
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The Role of Vitamin A in Brown Fat Activity and Energy Metabolism

Conditions
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Brown Adipose Tissue

Intervention / Treatment
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* Other: Cold exposure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20 - 45 years. Body mass index (BMI) 18.5 - 24.9 kg/m2 (lean) or 30.0 - 38.0 kg/m2 (obese) Exclusion Criteria: Endocrine (except hyperlipidemia), cardiovascular (except hypertension), liver, kidney, inflammatory bowel, rheumatic, oncologic disease or any other chronic condition. Medication for any of the above mentioned conditions. Pregnancy Metallic implants that are not MRI compatible

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lean<br>Cold exposure | Other: Cold exposure<br> <br> |
| Experimental: Obese<br>Cold exposure | Other: Cold exposure<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between retinol/retinol-binding protein concentrations and cold-induced brown fat acitivity | A possible association between serum retinol and retinol-binding protein concentrations and cold-induced brown fat activity in lean and obese subjects, respectively, will be analyzed. | 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analyses of potential BAT or browning markers in humans |  | 6 years | 
| Association between BAT activity and energy expenditure |  | 6 years | 
| Identification of new factors related to brown fat function | This is a very exploratory aim that involves a number of molecular tests. Therefore no single outcome measure can be defined here. Briefly, we will perform mRNA and miRNA analyses from BAT biopsies and plasma before and after cold exposure to identify new factors related to BAT function. Potential candidates will be tested in loss- or gain-of-function models in isolated human and/or murine adipocytes. In addition, the thermogenic effects of commercially available peptides, hormones, lipids, or steroid acids, will be tested in primary adipocytes. | 6 years |