Peripheral circadian rhythms in the liver and white adipose tissue of mice are attenuated by constant light and restored by time-restricted feeding

PLoS One. 2020 Jun 12;15(6):e0234439. doi: 10.1371/journal.pone.0234439. eCollection 2020.

Abstract

Disturbance of circadian rhythms underlies various metabolic diseases. Constant light exposure (LL) is known to disrupt both central and peripheral circadian rhythms. Here, we attempted to determine whether the effects of LL are different between various peripheral tissues and whether time-restricted feeding restores the circadian rhythms especially in white adipose tissue (WAT). Six-week-old mice were subjected to three feeding regimes: ad libitum feeding under light/dark phase (LD), ad libitum feeding under LL cycle, and restricted feeding at night-time under LL cycle with a normal chow. After 3 weeks, we compared body weight, food intake, plasma levels of lipids and glucose, and the expression patterns of the clock genes and the genes involved in lipid metabolism in the liver and WAT. The mice kept under LL with or without time-restricted feeding were 5.2% heavier (p<0.001, n = 16) than the mice kept under LD even though the food intakes of the two groups were the same. Food intake occurred mostly in the dark phase. LL disrupted this pattern, causing disruptions in circadian rhythms of plasma levels of triglycerides (TG) and glucose. Time-restricted feeding partially restored the rhythms. LL eliminated the circadian rhythms of the expression of the clock genes as well as most of the genes involved in lipid metabolism in both liver and WAT. More notably, LL markedly decreased not only the amplitude but also the average levels of the expression of the genes in the liver, but not in the WAT, suggesting that transcription in the liver is sensitive to constant light exposure. Time-restricted feeding restored the circadian rhythms of most of the genes to various degrees in both liver and WAT. In conclusion, LL disrupted the peripheral circadian rhythms more severely in liver than in WAT. Time-restricted feeding restored the circadian rhythms in both tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / metabolism
  • Animals
  • Circadian Rhythm / physiology*
  • Circadian Rhythm / radiation effects
  • Circadian Rhythm Signaling Peptides and Proteins / genetics*
  • Fasting / physiology*
  • Gene Expression Regulation / radiation effects
  • Light / adverse effects*
  • Lipid Metabolism / physiology*
  • Lipid Metabolism / radiation effects
  • Liver / metabolism
  • Male
  • Mice
  • Models, Animal
  • Photoperiod

Substances

  • Circadian Rhythm Signaling Peptides and Proteins

Grants and funding

This work was supported by a Grant-in-Aid for Scientific Research and MEXT-Supported Program for the Strategic Research Foundation at Private Universities 2011-2015 “Cooperative Basic and Clinical Research on Circadian Medicine” from the Ministry of Education, Culture, Sports, Science and Technology of Japan.