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“Love burns fat”––Oxytocinergic neural pathway that promotes fat combustion identified
Akihiro Fukushima (Kazuhiro Nakamura)

Oxytocin, a neuropeptide also known as “love hormone” or “trust hormone”, is released in the brain during social experiences (mating, parenting, being touched by conspecifics etc.) to modulate the behaviors. Besides the social effect, it has also been suggested that oxytocin stimulates sympathetic heat production (thermogenesis) in brown adipose tissue (BAT) and, as a result, increases whole-body metabolism. However, the central mechanism that functionally connects oxytocin and the sympathetic nervous system remains unclear.
To address this question, we developed a new adeno-associated virus vector to express genes of interest selectively in oxytocinergic neurons and found that oxytocinergic neurons in the paraventricular hypothalamic nucleus (PVH) project onto sympathetic premotor neurons in the rostral medullary raphe region (rMR). An action of oxytocin in the rMR elicited BAT thermogenesis and increased heart rate. Interestingly, optogenetic stimulation of oxytocinergic neurons in the PVH potentiated BAT thermogenesis and tachycardia evoked by an injection of NMDA, a glutamate receptor agonist, into the rMR. These results indicate that oxytocin released in the rMR not only drives BAT thermogenesis by itself, but also potentiates sympathetic thermogenic responses evoked by signals from other brain regions, including the dorsomedial hypothalamus.
Since oxytocin is released by social interactions, its sympathoexcitatory actions may be involved in emotion-related autonomic responses. Furthermore, given that BAT thermogenesis combusts fat, the PVH→rMR oxytocinergic neural pathway may be a potential target for preventing obesity.

An oxytocinergic neural pathway that stimulates thermogenic and cardiac sympathetic outflow.
Fukushima A, Kataoka N, Nakamura K.
Cell Reports 40 (12): 111380, 2022.

<Figure Legends>
A schematic diagram of PVH→rMR oxytocinergic neural pathway controlling BAT thermogenesis: PVH oxytocinergic neurons project onto sympathetic premotor neurons in the rMR (green in the upper diagram) and release oxytocin to activate premotor neurons. The activated premotor neurons drive BAT thermogenesis and increase heart rate (magenta in the upper diagram). Nanoinjection of oxytocin into the rMR elicited thermogenic sympathetic responses, and optogenetic stimulation of oxytocinergic neurons also potentiated NMDA-evoked thermogenic responses (lower diagram). The oxytocin-induced activation of sympathetic thermogenesis promotes fat combustion. BAT SNA, BAT sympathetic nerve activity; DMH, dorsomedial hypothalamus.

Department of Integrative Physiology, Graduate School of Medicine, Nagoya University, Japan