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

Anne-Loes Opperhuizen,Martijs Jonker,Ewout Foppen,Andries Kalsbeek,Michel Van Weeghel,Paul Wackers,Eric Fliers,Linda Van Kerkhof,Martijn Van Faassen

doi:10.3389/fnins.2019.00647

Abstract

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.

Highlights

Nowadays, artificial light competes with the importance of sunlight for determining the timing of human daily activities
In 2009 we showed that 1 h of Light exposure at night (LAN) exposure caused an upregulation of phosphoenolpyruvate carboxykinase, an important enzyme for glucose production, mRNA expression in the rat liver (Cailotto et al, 2009)
All experimental procedures performed were in accordance with the Council Directive 2010/63EU of the European Parliament and the Council of 22 September 2010 on protection of animals used for scientific purposes

Summary

Introduction

Artificial light competes with the importance of sunlight for determining the timing of human daily activities. In 2009 we showed that 1 h of LAN exposure caused an upregulation of phosphoenolpyruvate carboxykinase, an important enzyme for glucose production, mRNA expression in the rat liver (Cailotto et al, 2009). Together these data suggest that the liver is important for the effects of artificial light at night on glucose tolerance

Objectives

Methods

Results

Conclusion