A brain-to-liver signal mediates the inhibition of liver regeneration under chronic stress in mice

作者：Yanyu Zhou, Xiaoqi Lin, Yingfu Jiao, Dan Yang, Zhengyu Li, Ling Yin Zhu, Yixuan Li, Suqing Yin, Quanfu Li, Saihong Xu, Dan Tang, Song Zhang, Weifeng Yu, Po Gao, Liqun Yang · 发表于：Nature Communications · 年份：2024 · DOI：10.1038/s41467-024-54827-5 · 被引用次数：28 · 研究领域：Liver physiology and pathology、Liver Disease and Transplantation、Organ Transplantation Techniques and Outcomes

As the ability of liver regeneration is pivotal for liver disease patients, it will be of high significance and importance to identify the missing piece of the jigsaw influencing the liver regeneration. Here, we report that chronic stress impairs the liver regeneration capacity after partial hepatectomy with increased mortality in male mice. Anatomical tracing and functional mapping identified a neural circuit from noradrenergic neurons in the locus coeruleus (LC) to serotonergic neurons in the rostral medullary raphe region (rMR), which critically contributes to the inhibition of liver regeneration under chronic stress. In addition, hepatic sympathetic nerves were shown to be critical for the inhibitory effects on liver regeneration by releasing norepinephrine (NE), which acts on adrenergic receptor β2 (ADRB2) to block the proinflammatory macrophage activation. Collectively, we reveal a “brain-to-liver” neural connection that mediates chronic stress-evoked deficits in liver regeneration, thus shedding important insights into hepatic disease therapy. Whether and how chronic stress, often experienced by patients with chronic liver disease, affects liver regeneration remains mysterious. Here, authors show a “brain-to-liver” neural connection that mediates chronic stress-evoked deficits in liver regeneration.