Brown Adipose Tissue
Conditions
Brief summary
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.
Interventions
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between retinol/retinol-binding protein concentrations and cold-induced brown fat acitivity | 6 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 6 years | 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. |
Countries
Austria