Dim Light at Night Disturbs Molecular Pathways of Lipid Metabolism.

Monika Okuliarova,Katarina Stebelova,Valentina Sophia Rumanova,Michal Zeman

doi:10.3390/ijms21186919

Monika Okuliarova, Katarina Stebelova + Show 2 more

Open Access

https://doi.org/10.3390/ijms21186919

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Abstract

Dim light at night (dLAN) is associated with metabolic risk but the specific effects on lipid metabolism have only been evaluated to a limited extent. Therefore, to explore whether dLAN can compromise lipid metabolic homeostasis in healthy individuals, we exposed Wistar rats to dLAN (~2 lx) for 2 and 5 weeks and analyzed the main lipogenic pathways in the liver and epididymal fat pad, including the control mechanisms at the hormonal and molecular level. We found that dLAN promoted hepatic triacylglycerol accumulation, upregulated hepatic genes involved in de novo synthesis of fatty acids, and elevated glucose and fatty acid uptake. These observations were paralleled with suppressed fatty acid synthesis in the adipose tissue and altered plasma adipokine levels, indicating disturbed adipocyte metabolic function with a potential negative impact on liver metabolism. Moreover, dLAN-exposed rats displayed an elevated expression of two peroxisome proliferator-activated receptor family members (Pparα and Pparγ) in the liver and adipose tissue, suggesting the deregulation of important metabolic transcription factors. Together, our results demonstrate that an impaired balance of lipid biosynthetic pathways caused by dLAN can increase lipid storage in the liver, thereby accounting for a potential linking mechanism between dLAN and metabolic diseases.

Highlights

Hepatic lipid homeostasis is maintained through a balance among metabolic pathways controlling the handling of triacylglycerols (TAGs) and fatty acids in the liver [1]
We found that nocturnal exposure to low-intensity light promoted hepatic TAG accumulation, which was associated with enhanced de novo synthesis of fatty acids and elevated glucose and fatty acid uptake into the liver
To examine the molecular mechanisms of Dim light at night (dLAN)-induced metabolic effects, we focused on the peroxisome proliferator-activated receptors (PPARs) family of nuclear receptors that function as transcription factors in many aspects of lipid and glucose metabolism [6]

Summary

Introduction

Hepatic lipid homeostasis is maintained through a balance among metabolic pathways controlling the handling of triacylglycerols (TAGs) and fatty acids in the liver [1] This balance is a tightly regulated system of signaling and transcriptional networks, and its disruption can lead to excessive lipid accumulation that, in turn, may progress to nonalcoholic fatty liver disease (NAFLD) [1,2,3]. Rate-limiting enzymes for de novo lipogenesis are acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN), which catalyze the first steps in the fatty acid synthesis [5] Both are transcriptionally regulated by various nuclear receptors, including peroxisome proliferator-activated receptors (PPARs), which represent important regulators of lipid metabolic pathways in different body tissues [6]

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Discussion

Conclusion