Time-restricted feeding attenuates hypercholesterolaemia and atherosclerosis development during circadian disturbance in APOE∗3-Leiden.CETP miceResearch in context
Wietse In Het Panhuis,
Milena Schönke,
Melanie Modder,
Hannah E. Tom,
Reshma A. Lalai,
Amanda C.M. Pronk,
Trea C.M. Streefland,
Linda W.M. van Kerkhof,
Martijn E.T. Dollé,
Marie A.C. Depuydt,
Ilze Bot,
Winnie G. Vos,
Laura A. Bosmans,
Bram W. van Os,
Esther Lutgens,
Patrick C.N. Rensen,
Sander Kooijman
Affiliations
Wietse In Het Panhuis
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
Milena Schönke
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
Melanie Modder
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
Hannah E. Tom
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
Reshma A. Lalai
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
Amanda C.M. Pronk
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
Trea C.M. Streefland
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
Linda W.M. van Kerkhof
Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Martijn E.T. Dollé
Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Marie A.C. Depuydt
Leiden Academic Centre for Drug Research, Division of Biotherapeutics, Leiden University, Leiden, the Netherlands
Ilze Bot
Leiden Academic Centre for Drug Research, Division of Biotherapeutics, Leiden University, Leiden, the Netherlands
Winnie G. Vos
Department of Medical Biochemistry, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, the Netherlands; Amsterdam Immunity and Infection, Amsterdam, the Netherlands
Laura A. Bosmans
Department of Medical Biochemistry, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, the Netherlands; Amsterdam Immunity and Infection, Amsterdam, the Netherlands
Bram W. van Os
Department of Medical Biochemistry, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, the Netherlands; Amsterdam Immunity and Infection, Amsterdam, the Netherlands
Esther Lutgens
Department of Medical Biochemistry, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, the Netherlands; Amsterdam Immunity and Infection, Amsterdam, the Netherlands; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
Patrick C.N. Rensen
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
Sander Kooijman
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands; Corresponding author. Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
Summary: 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.
