Conditional Tissue Ablation of the Brown Adipose Tissue: Transadipogenesis, Thermogenesis and Energy Homeostasis

초록

The brown adipose tissue (BAT) roles as a major site of non-shivering thermogenesis important for the regulation of the body temperature and body weight. In addition, BAT has also been suggested to play a role in energy homeostasis through its endocrine function. However, there are important questions surrounding, for example, the differentiation of white adipose tissue (WAT) vs. BAT, the function of BAT in obesity, and the role of neonatal BAT in which no white adipose tissue is formed. To understand these functional aspects of BAT, we produced a transgenic mouse line in which BAT could express HSV-TK from the UCP1 promoter and be conditionally ablated by administrating Ganciclovir (GCV). The expression of HSV-TK transgene was mild but BAT specific in our transgenic mice. Treatment of GCV to adult mice caused functional atrophy of brown adipocytes leading to transdifferentiation into white adipocytes. On the contrary, UCP-TK neonates from the GCV-treated pregnant mice died after birth with defects in energy metabolism of liver as well as the function of BAT.