Role of brown adipose tissue (BAT) in energy balance

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

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.