Role of brown adipose tissue (BAT) in energy balance

总结： 热生物学在小型和大型哺乳动物之间是不同的。在典型的周围环境温度下（例如，22 ℃），小鼠超过三分之一的能量消耗用于维持核心体温，主要是通过棕色脂肪组织（BAT）。为了保存能量，小鼠可以进入调节性低温，而人类则不行。由于人类消耗很少或没有能量专门用于保暖，在30 ℃（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，质子载体二硝基苯酚和β 3肾上腺素能激动剂CL 316243都能在热中性时增加代谢率，但只有CL 316243在22 ℃时增加代谢率。在30 ℃下饲养的小鼠也可能比在22 ℃下饲养的小鼠更肥胖。必须了解环境温度的影响，以确保小鼠实验适用于人类肥胖。 BAT也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。 二零二三财年的进展包括以下各项： 我们正在继续研究表达BRS 3（POA-BRS 3）神经元的视前区神经元亚群，这些神经元的激活会增加体温;相反，这些神经元的急性抑制会降低体温。我们还开始探索由Hrh 1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Otop 1（Otopetrin 1）的作用，这是一种在棕色脂肪组织中高度表达的质子选择性通道。主要方法是比较野生型和Otop 1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.