New targets on the BATtlefield of Obesity
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Obesity is an epidemic with major effects on health as it does increase the risk of cardiovascular diseases, diabetes and cancer. Obesity is described as excessive fat accumulation that occurs when energy intake exceeds energy expenditure. In the body excess energy can be stored in adipose tissue (AT). In classical view there are two types of AT; white adipose tissue (WAT) and brown adipose tissue (BAT). Main function of WAT is to store energy for future needs, a function mainly orchestrated by the white adipocytes. White adipocytes are characterised by peripheral organelles surrounding a big central lipid droplet. BAT on the other hand is composed of brown adipocytes, which have a central nucleus surrounded by multiple lipid droplets and several well-developed mitochondria. The presence of mitochondria gave the cell its brown colour and contribute to the main function of BAT, thermogenesis. Thermogenesis is carried out by uncoupling protein 1 (UCP1). Active UCP1 separates oxidative phosphorylation from ATP synthesis by pumping protons back into the mitochondrial matrix. As a result the energy is released as heat. AT is conserved among species, but the distribution is distinct. In mammals WAT and BAT can form specific depots. WAT depots are most abundant and can be either subcutaneous (under the skin) or visceral (surrounding organs). BAT depots are present in all newborn mammals, but in large mammals, like humans, after birth the depots will be replaced by WAT. Studies on white and brown adipocytes revealed that the cells had different developmental origins. The interest in brown adipocyte biology increased after the observation that active BAT was present in human adults. Another striking observation was the presence of brown-like adipocytes in classical WAT depots. These cells can show several brown adipocyte characteristics, like UCP1 expression. However, gene expression profiles revealed that these brown-like adipocytes are distinct from classical brown adipocytes and they were called beige adipocytes. Previous observation was made in a mouse model. To test whether the observed BAT depots in human adults consists of classical brown or beige adipocytes, the gene expression profiles of these particular cells were compared. The outcome of this study was striking, since the adipocytes in human BAT showed resemblance with murine beige cells and not with the classical brown adipocytes. In addition to these new insights in adipocyte biology, BAT activity was observed to be a protective factor for obesity. Although not yet elucidated BAT might exert this protective function via increased energy expenditure by thermogenesis. Altogether, this knowledge had led to new therapeutic approaches to combat obesity via induction of BAT or beige cells.