Although obesity is associated with higher risk of cardiometabolic disease, high-protein diets can reduce fatness but still promote cardiometabolic disease. Zhang et al. address this contradiction and show that high-protein diets, and subsequently higher blood leucine levels, promote mTORC1 activation in macrophages in humans and mice, and that an increase in dietary leucine raises the risk of atherosclerosis in a mouse model.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Single-cell RNA sequencing in human atherosclerotic plaques reveals a novel smooth muscle cell subtype that possesses multi differentiation potential and shapes the microenvironment
Clinical and Experimental Medicine Open Access 16 July 2025
-
Metabolic regulation of the immune system in health and diseases: mechanisms and interventions
Signal Transduction and Targeted Therapy Open Access 09 October 2024
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 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Fappi, A. & Mittendorfer, B. Curr. Opin. Clin. Nutr. Metab. Care 23, 380–386 (2020).
Abdelaal, M., le Roux, C. W. & Docherty, N. G. Ann. Transl. Med. 5, 161 (2017).
Zhang, X. et al. Nat. Metab. 2, 110–125 (2020).
Zhang, X. et al. Nat. Metab. https://doi.org/10.1038/s42255-024-00984-2 (2023).
Wolfson, R. L. & Sabatini, D. M. Cell Metab. 26, 301–309 (2017).
Wahren, J., Felig, P. & Hagenfeldt, L. J. Clin. Invest. 57, 987–999 (1976).
Fontana, L. et al. Cell Rep. 16, 520–530 (2016).
Solon-Biet, S. M. et al. Nat. Metab. 1, 532–545 (2019).
Yap, Y. W. et al. Nat. Commun. 11, 2894 (2020).
Yu, D. et al. Cell Metab. 33, 905–922.e6 (2021).
Lee, M. K. S. et al. Trends Endocrinol. Metab. 31, 525–535 (2020).
Solon-Biet, S. M. et al. Cell Metab. 19, 418–430 (2014).
Green, C. L. et al. Cell Metab. 34, 209–226.e5 (2022).
Mitchell, S. J. et al. Cell Metab. 23, 1093–1112 (2016).
Freudenberg, A., Petzke, K. J. & Klaus, S. J. Nutr. Biochem. 23, 1524–1530 (2012).
Acknowledgements
We acknowledge funding from the National Health and Medical Research Council of Australia (ID: 2020757) to A.J.R. and from the Diabetes Australia Research Program (Y24G-RUSP) to P.M.R. and A.J.R.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
A.J.R. and P.M.R. receive research funds from Boehringer-Ingelheim, a pharmaceutical company, for an unrelated research project.
Rights and permissions
About this article
Cite this article
Rose, A.J., Rusu, P.M. A leucine–macrophage mTORC1 connection drives increased risk of atherosclerosis with high-protein diets. Nat Metab 6, 203–204 (2024). https://doi.org/10.1038/s42255-023-00952-2
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s42255-023-00952-2
This article is cited by
-
Single-cell RNA sequencing in human atherosclerotic plaques reveals a novel smooth muscle cell subtype that possesses multi differentiation potential and shapes the microenvironment
Clinical and Experimental Medicine (2025)
-
Metabolic regulation of the immune system in health and diseases: mechanisms and interventions
Signal Transduction and Targeted Therapy (2024)
