Data_Sheet_1_Effects of Light-at-Night on the Rat Liver – A Role for the Autonomic Nervous System.docx

Exposure to light at night (LAN) has been associated with serious pathologies, including obesity, diabetes and cancer. Recently we showed that 2 h of LAN impaired glucose tolerance in rats. Several studies have suggested that the autonomic nervous system (ANS) plays an important role in communicating these acute effects of LAN to the periphery. Here, we investigated the acute effects of LAN on the liver transcriptome of male Wistar rats. Expression levels of individual genes were not markedly affected by LAN, nevertheless pathway analysis revealed clustered changes in a number of endocrine pathways. Subsequently, we used selective hepatic denervations [sympathetic (Sx), parasympathetic (Px), total (Tx, i.e., Sx plus Px), sham] to investigate the involvement of the ANS in the effects observed. Surgical removal of the sympathetic or parasympathetic hepatic branches of the ANS resulted in many, but small changes in the liver transcriptome, including a pathway involved with circadian clock regulation, but it clearly separated the four denervation groups. On the other hand, analysis of the liver metabolome was not able to separate the denervation groups, and only 6 out of 78 metabolites were significantly up- or downregulated after denervations. Finally, removal of the sympathetic and parasympathetic hepatic nerves combined with LAN exposure clearly modulated the effects of LAN on the liver transcriptome, but left most endocrine pathways unaffected.
Conclusion: One-hour light-at-night acutely affects the liver transcriptome. Part of this effect is mediated via the nervous innervation, as a hepatectomy modulated and reduced the effect of LAN on liver transcripts.

夜间光照（Light at Night, LAN）已被证实与肥胖、糖尿病、癌症等多种严重病理状态密切相关。此前本团队研究显示，2小时夜间光照会损伤大鼠的葡萄糖耐量。多项研究表明，自主神经系统（Autonomic Nervous System, ANS）在将夜间光照的急性效应传递至外周组织的过程中发挥关键作用。本研究旨在探究夜间光照对雄性Wistar大鼠肝脏转录组的急性影响。单个基因的表达水平未受夜间光照的显著影响，但通路分析显示，多条内分泌通路出现成簇的表达变化。随后，本研究采用选择性肝脏去神经支配术[交感神经去支配（Sympathetic denervation, Sx）、副交感神经去支配（Parasympathetic denervation, Px）、完全去支配（Total denervation, Tx，即Sx联合Px）、假手术对照组（Sham）]，以探究自主神经系统在上述观测效应中的参与机制。对自主神经系统的肝脏交感或副交感分支进行手术切除后，大鼠肝脏转录组出现诸多小幅表达变化，其中包含一条与生物钟调控相关的通路，且该处理可清晰区分四组去神经支配大鼠。另一方面，肝脏代谢组分析无法区分各组去神经支配大鼠，且仅78种代谢物中有6种在去神经支配术后出现显著上调或下调。最后，联合实施肝脏交感与副交感神经切除并辅以夜间光照处理，可显著调控夜间光照对肝脏转录组的效应，但多数内分泌通路的表达未受影响。结论：1小时夜间光照可急性调控肝脏转录组。该效应部分通过神经支配介导，因肝脏去神经支配术可调控并削弱夜间光照对肝脏转录本的影响。