Role of brown adipose tissue (BAT) in energy balance

小型和大型哺乳动物的热生物学是不同的。在典型的环境温度下(例如：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）。为了保存能量，老鼠可以进入有调节的低体温状态，而人类则不会。由于人类很少或根本不消耗能量来保持温暖，在30摄氏度（接近热中性）下研究的小鼠可能是人类能量稳态的更好模型。在小鼠中，原体二硝基苯酚和β -肾上腺素能激动剂CL316243在热中性时均增加代谢率，但只有CL316243在22℃时增加代谢率。30℃环境下的小鼠也可能比22℃环境下的小鼠更肥胖。

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.