Mechanisms
Time-restricted eating reduces atherosclerotic lesion size and inflammatory cell content in CETP-humanised mice during simulated shift-work (EBioMedicine 2023)
Original title: Time-restricted feeding attenuates hypercholesterolaemia and atherosclerosis development during circadian disturbance in APOE∗3-Leiden.CETP mice
In female APOE∗3-Leiden.CETP mice, a humanised model expressing human cholesteryl ester transfer protein (CETP), circadian disturbance was induced by repeated 6-hour phase advances of the light-dark cycle to mimic shift work. Time-restricted feeding (TRF), limiting food access to the dark phase, did not prevent the rise in circulating inflammatory monocytes or postprandial plasma triglycerides caused by circadian disturbance. However, TRF reduced atherosclerotic lesion size, prevented an increase in lesion macrophage content, increased anti-inflammatory monocytes, prevented T cell activation, and lowered plasma total cholesterol and markers of hepatic cholesterol synthesis, independent of total food intake. The findings support time-restricted eating as a candidate strategy to reduce atherosclerotic cardiovascular disease risk in shift workers.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.