Vitamin A in Brown Fat Activity

Medical University of Vienna66 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Brown Adipose Tissue

Interventions

Eligibility

Sex: ALLMin age: 20 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 6 years

Secondary Outcomes

Analyses of potential BAT or browning markers in humans

Time frame: 6 years

Association between BAT activity and energy expenditure

Time frame: 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.

Time frame: 6 years

Vitamin A in Brown Fat Activity

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes