Role of brown adipose tissue (BAT) in energy balance

热生物学在小型和大型哺乳动物之间是不同的。在典型的环境温度(例如22摄氏度)下，小鼠超过三分之一的能量消耗用于维持核心体温，主要是棕色脂肪组织(BAT)。为了节省能量，小鼠可以进入规定的低温状态，而人类则不能。由于人类很少或根本不花费能量来保暖，在30摄氏度(接近中温)下研究的小鼠可能是研究人类能量动态平衡的更好模型。在小鼠中，原载体二硝基苯酚和β3肾上腺素能激动剂CL316243都能在中温下增加代谢率，但只有CL316243在22℃时增加了代谢率。 BAT还与体温过低密切相关，因为体温过低的诱导涉及BAT的完全失活，而恢复则会重新激活它。因此，对导致体温过低的药物的研究应该在有助于调节和控制BAT的神经通路中相互作用。 2020财年的进展包括： 在2019财年，我们报道了急性激活下丘脑背内侧(DMHBrs3)表达Brs3的神经元，增加了体温、棕色脂肪组织温度、能量消耗、心率和血压，而对食物摄入量和体力活动没有影响。相反，激活下丘脑室旁核中的Brs3神经元对TB或能量消耗没有影响，但抑制了食物的摄入。我们目前正在研究Brss3表达的神经元在视前区的作用。

Thermal biology is different between small and large mammals. At typical ambient environmental temperature (eg., 22 C), over one third of energy expenditure in mice is devoted to maintaining core body temperature, largely by brown adipose tissue (BAT). To conserve energy, mice can enter a regulated hypothermia, while humans do not. Since humans expend little or no energy specifically to keep warm, mice studied at 30 C (near thermoneutrality) may be a better model for human energy homeostasis. In mice, dinitrophenol, a protonophore, and CL316243, a beta3-adrenergic agonist, both increased metabolic rate at thermoneutrality but only CL316243 increased it at 22 C. Mice housed at 30 C also may become more obese than mice at 22 C. The effect of environmental temperature must be understood to ensure applicability of mouse experiments to human obesity. BAT is also intimately involved with hypothermia, as induction of hypothermia involves complete inactivation of BAT, while recovery reactivates it. Thus, studies of drugs causing hypothermia should interact in the neural pathways that contribute to the regulation and control of BAT. Progress in FY2020 includes the following: In FY 2019, we reported that acute activation of Brs3-expressing neurons in the dorsomedial hypothalamus (DMHBrs3) increased body temperature, brown adipose tissue temperature, energy expenditure, heart rate, and blood pressure, with no effect on food intake or physical activity. Conversely, activation of Brs3 neurons in the paraventricular nucleus of the hypothalamus had no effect on Tb or energy expenditure, but suppressed food intake. We are currently doing studies on the role of Brss3-expressing neurons in the preoptic area.