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Atherosclerosis

A leucine–macrophage mTORC1 connection drives increased risk of atherosclerosis with high-protein diets

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.

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Fig. 1: High-protein diets promote mTORC1 signalling in macrophages, and atherosclerosis risk, though elevated leucine.

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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.

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Correspondence to Adam J. Rose.

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A.J.R. and P.M.R. receive research funds from Boehringer-Ingelheim, a pharmaceutical company, for an unrelated research project.

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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

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