New perspectives on the significance of brown adipose tissue in mammals

Although textbook knowledge inevitable associates brown adipose tissue with cold and body temperature regulation (regulatory thermogenesis), we are far from understanding how, why and when Eutherian mammals gained full UCP1-mediated thermogenic support. Brown adipose tissue is also present in humans, and it is currently considered a major therapeutic target in the treatment of obesity. To fully appreciate and to potentially modulate the function of this unique tissue, comparative studies from nature’s toolbox will prove invaluable new insights. In my PhD-thesis I therefore sought to expand our knowledge on brown adipose tissue thermogenesis and its significance in various mammalian orders, spanning from the in vitro to the in vivo level. In doing so, I aimed to uncover novel aspects regarding the evolution of its thermogenic function. In my studies, I used artificially generated UCP1-ablated mice to evaluate further benefits of UCP1 expression on brown adipose tissue function (ROS prevention) and the torpor behavior of Eutherian mammals from Holartic regions. Furthermore I tried to clarify the function of UCP1-mediated nonshivering thermogenesis in more “ancient” mammals from Afrotropical regions, is brown adipose tissue of Afrotherians seasonally regulated? Therefore I worked with two members of the Afrotherian clade, Western rock elephant shrews (Elephantulus rupestris) and protoendothermic Lesser hedgehog tenrecs (Echinops telfairi). The later additionally provided me the perfect model organism for another approach; the function of brown adipose tissue in protoendothermic mammals and the revealing of selection constraints that supported the evolution of brown adipose tissue and mammalian endothermy. Specifically, the following questions were addressed: 1.What are the effects of UCP1 activity on the torpor behavior of Eutherian mammals, can they arouse from hypometabolic and hypothermic states (torpor) without UCP1-mediated nonshivering thermogenesis? If so, what are the benefits of UCP1 activity for arousal? 2.Does UCP1 play a role in the prevention of reactive oxygen species during nonshivering thermogenesis? Was the prevention of ROS the ancient function of UCP1? 3.Do species from the Afrotropics adjust their thermoregulatory capacities during winter? Is nonshivering thermogenesis in Western rock elephant shrews adaptive and a common feature of the Afrotherian clade? 4.Do protoendothermic Lesser hedgehog tenrecs possess functional brown adipose tissue and adaptive thermogenesis? If so, is the specific function of UCP1 comparable between protoendothermic and endothermic mammals? 5.Was brown adipose tissue involved in the evolution of endothermy?