Consumption of a high-fat diet leads to the progressive growth of atherosclerotic lesions. Two new studies document that, despite similar overall exposure to high-fat diet over a lifetime, an intermittent consumption of high-fat diet early in life accelerates atherosclerosis compared with continuous consumption of a high-fat diet. The mechanisms for accelerated atherosclerosis include reprogramming of macrophages and neutrophils.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$32.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout

References
Ference, B. A., Graham, I., Tokgozoglu, L. & Catapano, A. L. Impact of lipids on cardiovascular health: JACC health promotion series. J. Am. Coll. Cardiol. 72, 1141–1156 (2018).
Borén, J. et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 41, 2313–2330 (2020).
Takaoka, M. et al. Early intermittent hyperlipidaemia alters tissue macrophages to fuel atherosclerosis. Nature 634, 457–465 (2024).
Lavillegrand, J. R. et al. Alternating high-fat diet enhances atherosclerosis by neutrophil reprogramming. Nature 634, 447–456 (2024).
Zernecke, A. et al. Integrated single-cell analysis-based classification of vascular mononuclear phagocytes in mouse and human atherosclerosis. Cardiovasc. Res. 119, 1676–1689 (2023).
Swirski, F. K. et al. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J. Clin. Invest 117, 195–205 (2007).
Swirski, F. K. & Nahrendorf, M. Cardioimmunology: the immune system in cardiac homeostasis and disease. Nat. Rev. Immunol. 18, 733–744 (2018).
Silvestre-Roig, C., Braster, Q., Ortega-Gomez, A. & Soehnlein, O. Neutrophils as regulators of cardiovascular inflammation. Nat. Rev. Cardiol. 17, 327–340 (2020).
Liu, Z. et al. Fate mapping via Ms4a3-expression history traces monocyte-derived cells. Cell 178, 1509–1525.e19 (2019).
Nielsen, S. F. & Nordestgaard, B. G. Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study. Eur. Heart J. 37, 908–916 (2016).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Swirski, F.K., Binder, C.J. Lower your cholesterol early, and stick with it!. Nat Rev Cardiol 22, 69–70 (2025). https://doi.org/10.1038/s41569-024-01095-x
Published:
Issue date:
DOI: https://doi.org/10.1038/s41569-024-01095-x