Role of brown adipose tissue (BAT) in energy balance

摘要： 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。 2023财年的进展包括： 我们正在继续研究表达Brs3(POA-Brs3)神经元的视前区神经元亚群，这些神经元的激活会提高体温；相反，对这些神经元的急性抑制会降低体温。我们还开始探索由HRH1基因编码的组胺-1受体的作用。 另一个正在进行的项目旨在了解Otop1(Otopetrin 1)的作用，Otopetrin 1是一种质子选择性通道，在棕色脂肪组织中高度表达。主要方法是比较野生型和Otop1基因敲除小鼠。

Summary: 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 FY2023 includes the following: We are continuing to study subpopulations of preoptic area neurons expressing BRS3 (POA-BRS3) neurons whose activation increased body temperature; inversely, acute inhibition of these neurons reduced body temperature. We have also begun to explore the role of histamine-1 receptors, encoded by the Hrh1 gene. Another ongoing project is aimed at understanding the role of Otop1 (Otopetrin 1), a proton-selective channel that is highly expressed in brown adipose tissue. The main approach is comparison of wild-type and Otop1 knockout mice.