HEDESAN Oana

The Role of Vitamin A in the Brown Fat Activity and Energy Balance

Obesity is a global epidemic associated with multiple comorbidities such as diabetes mellitus and cardiovascular disease. Through its heat-generating properties, the brown adipose tissue (BAT) provides the main defense mechanism against hypothermia and excessive feeding in rodents. As a result of the oxidation of fatty acids, BAT dissipates energy through the production of heat. This process is called uncoupled respiration and is mediated by a tissue-specific protein called uncoupling protein 1 (UCP-1). The recent discovery of BAT in adult humans has led to a series of attempts that aim to enhance the activation of this tissue. The  merging importance of BAT has focused a particular attention on manipulating  dipose metabolic pathways in order to favor energy expenditure as a novel approach to combat obesity. Recent preclinical studies suggest vitamin A (retinol) as a nutrient critically involved in the function of the BAT and energy metabolism in rodents. However, the role of retinol in human brown adipose tissue function is completely unknown. The central issue addressed in this thesis is the relationship between systemic retinoid concentrations and brown fat activity. In order to accomplish this objective a clinical trial including 76 subjects was designed. The subjects will be included after a screening visit, if the inclusion criteria are met. The study population will be divided into a group of lean subjects and a group of obese subjects. We will determine the association between systemic retinol/retinol binding protein (RBP) concentrations and brown fat activity. Therefore retinol and RBP will be measured at baseline (room temperature) followed by [18F]FDG-PET/CT and [18F]FDG-PET/MR scans on study day 1. These tests will be repeated on study 2 but this time subjects will undergo moderate cold exposure using a cooling vest prior to the analyses. As secondary outcome parameters we will determine cold-mediated changes in retinoid  concentrations and potential differences between lean and obese subjects. It is widely accepted that the activation of BAT leads to increased energy expenditure. Therefore, I will also investigate any association between the basal metabolic rate before and after cold exposure and altered retinoid concentration. Pursuing these aims we endeavor to define the role of vitamin A in human brown fat physiology and energy balance.

Methods and Skills:

clinical studies; Western blotting; PCR; cell culture