Time-restricted feeding attenuates hypercholesterolaemia and atherosclerosis development during circadian disturbance in APOE∗3-Leiden.CETP mice

EBioMedicine. 2023 Jul:93:104680. doi: 10.1016/j.ebiom.2023.104680. Epub 2023 Jun 23.

Abstract

Background: Circadian disturbance (CD) is the consequence of a mismatch between endogenous circadian rhythms, behaviour, and/or environmental cycles, and frequently occurs during shift work. Shift work has been associated with elevated risk for atherosclerotic cardiovascular disease (asCVD) in humans, but evidence for the effectiveness of prevention strategies is lacking.

Methods: Here, we applied time-restricted feeding (TRF) as a strategy to counteract atherosclerosis development during CD in female APOE∗3-Leiden.CETP mice, a well-established model for humanized lipoprotein metabolism. Control groups were subjected to a fixed 12:12 h light-dark cycle, while CD groups were subjected to 6-h phase advancement every 3 days. Groups had either ad libitum (AL) access to food or were subjected to TRF with restricted food access to the dark phase.

Findings: TRF did not prevent the increase in the relative abundance of circulating inflammatory monocytes and elevation of (postprandial) plasma triglycerides during CD. Nonetheless, TRF reduced atherosclerotic lesion size and prevented an elevation in macrophage content of atherosclerotic lesions during CD, while it increased the relative abundance of anti-inflammatory monocytes, prevented activation of T cells, and lowered plasma total cholesterol levels and markers of hepatic cholesterol synthesis. These effects were independent of total food intake.

Interpretation: We propose that time restricted eating could be a promising strategy for the primary prevention of asCVD risk in shift workers, which warrants future study in humans.

Funding: This work was funded by the Novo Nordisk Foundation, the Netherlands Ministry of Social Affairs and Employment, Amsterdam Cardiovascular Sciences, and the Dutch Heart Foundation.

Keywords: Atherosclerotic cardiovascular disease; Circadian disturbance; Inflammation; Lipoprotein metabolism; Time-restricted feeding.

MeSH terms

  • Animals
  • Apolipoprotein E3 / genetics
  • Apolipoprotein E3 / metabolism
  • Atherosclerosis* / metabolism
  • Cholesterol
  • Cholesterol Ester Transfer Proteins
  • Circadian Rhythm / physiology
  • Female
  • Humans
  • Hypercholesterolemia* / complications
  • Mice
  • Photoperiod

Substances

  • Apolipoprotein E3
  • Cholesterol
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins