Invited Speaker 4th Metabolic Diseases; Breakthrough Discoveries in Diabetes & Obesity Meeting 2024

Critical role of brainstem NPFF neuronal circuits in the control of torpor-like states (#29)

Herbert Herzog 1 , Lei Zhang 1 , Julia Koller 1 , Ramon Tasan 2
  1. Faculty of Medicine, St Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia
  2. Department of Pharmacology, University of Innsbruck, Innsbruck, Austria

Energy conserving strategies such as torpor and hibernation are important survival mechanisms that endothermic organism utilise to deal with environmental challenges like starvation and cold exposure. While neuronal circuits in the brain have been implicated in this process the exact underlying mechanism of initiating and controlling torpor-like states is still unknown. We have now identified that selective chemogenetic activation of a brainstem NPFF neuronal circuit induces a hypothermic and hypometabolic state in mice, characterised by a rapid drop in brown adipose and whole-body temperature, reduced locomotor activity and altered glucose metabolism. Interestingly, although body temperature and oxygen consumption are low in this state, the mice are still able to adjust body temperature to environmental temperature fluctuations. Mechanistically, NTS NPFF neuronal activation modulates neurons in the lateral parabrachial nucleus (PBN) and median preoptic area (MPO) to reduce body temperature as well as alters parasympathetic outflow to control glucose metabolism. Taken together, our results reveal a specific neuronal circuit in the brain stem that serves as a major regulator of torpor, which may also be explored as potential intervention point in metabolic diseases.