Lipid metabolic adaptations during inflammation are controlled by the circadian clock and impaired by light at night

TL;DR

The body's ability to adapt its fat metabolism during inflammation is controlled by the circadian clock and disrupted by exposure to light at night.

Contribution

This study reveals how circadian clocks regulate lipid metabolism during inflammation and how this is impaired by dim light at night.

Findings

Fatty acid mobilization in visceral white adipose tissue was higher after daytime compared to nighttime LPS injection under normal light/dark cycles.

Disruption of the circadian rhythm by dim light at night impaired the body's lipid metabolic adaptations during inflammation.

Circadian clocks in the liver and adipose tissue showed time-of-day-dependent responses to LPS, linking them to metabolic and inflammatory regulation.

Abstract

Immune defence requires systemic metabolic changes to redirect energy and nutrients to activated immune cells. The circadian clock is known to control the immune response, but its role in regulating metabolic adaptations following the immune challenge remains poorly understood. We aimed to examine the inflammatory and metabolic responses in rat liver and visceral white adipose tissue (vWAT) after time-of-day-dependent endotoxin stimulation under a regular light/dark cycle or dim artificial light at night (ALAN; ~2 lx), which disrupts immune and metabolic rhythms. Male rats were challenged with lipopolysaccharide (LPS) either during the day or night and acute changes in metabolic pathways and the peripheral metabolic clocks were analysed at both systemic and molecular levels.

In the control light/dark cycle, we observed higher fatty acid (FA) mobilization in vWAT after daytime than nighttime LPS injection. Similarly, hepatic glucose metabolism was more responsive to daytime than nighttime LPS, while the opposite trend was observed for FA uptake and synthesis. This daily variability in metabolic changes was associated with the inflammatory response, involving nuclear factor interleukin-3 regulated (NFIL3) in the liver and nuclear factor-kappa B (NF-κB)/NLR family, pyrin domain containing 3 (NLRP3) inflammasome pathway in vWAT. Hepatic and adipose clocks also showed time-of-day-dependent response to LPS, indicating a direct link to circadian regulation. Disruption of metabolic clocks by ALAN impaired the capacity of rats to maintain lipid metabolic adaptations during inflammation.

Together, our results highlight the role of circadian clocks in LPS-induced responses of glucose and FA metabolism and their susceptibility to disruption by ALAN.

The online version contains supplementary material available at 10.1007/s00011-025-02066-9.

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