The source of dietary fat influences anti-tumour immunity in obese mice

Britta Kunkemoeller; Hannah Prendeville; Claire McIntyre; Ayantu Temesgen; Rόisín M. Loftus; Conghui Yao; Lydia Dyck; Linda V. Sinclair; Christina Rollings; Aaron Douglas; Gerard Pernes; Kathleen A.J. Mitchelson; Cathal Harmon; Mathilde Raverdeau; Ross Ward; Harry Kane; Jaclyn Kline; Katie L. O’Brien; Martin Brennan; Frances Smith; Brenneth Stevens; Helen M. Roche; Ed C. Lavelle; David K. Finlay; Doreen A. Cantrell; Edward T. Chouchani; Susan Kaech; Evanna L. Mills; Marcia Haigis; Lydia Lynch

doi:10.1038/s42255-025-01330-w

The source of dietary fat influences anti-tumour immunity in obese mice

Britta Kunkemoeller
, Hannah Prendeville
, Claire McIntyre
, Ayantu Temesgen
, Rόisín M. Loftus
, Conghui Yao
, Lydia Dyck
, Linda V. Sinclair
, Christina Rollings
, Aaron Douglas
, Gerard Pernes
, Kathleen A.J. Mitchelson
, Cathal Harmon
, Mathilde Raverdeau
, Ross Ward
, Harry Kane
, Jaclyn Kline
, Katie L. O’Brien
, Martin Brennan
, Frances Smith

Brenneth Stevens, Helen M. Roche, Ed C. Lavelle, David K. Finlay, Doreen A. Cantrell, Edward T. Chouchani, Susan Kaech, Evanna L. Mills, Marcia Haigis, Lydia Lynch (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

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Abstract

Obesity increases the risk of many cancers and impairs the anti-tumour immune response. However, little is known about whether the source or composition of dietary fat affects tumour growth or anti-tumour immunity in obesity. Here, we show that high-fat diets (HFDs) derived from lard, beef tallow or butter accelerate tumour growth in a syngeneic model of melanoma, but HFDs based on coconut oil, palm oil or olive oil do not, despite equivalent obesity. Using butter-based and palm oil-based HFDs as examples, we find that these dietary fat sources differentially regulate natural killer and CD8 T cell infiltration and function within the tumour microenvironment, governed by distinct effects on the plasma metabolome and intracellular metabolism. We identify diet-related lipid intermediates, namely long-chain acylcarnitine species, as immunosuppressive metabolites enriched in mice fed butter compared to palm oil HFD. Together, these results highlight the significance of diet in maintaining a healthy immune system and suggest that modifying dietary fat may improve cancer outcomes in obesity.

Original language	English
Pages (from-to)	1630-1645
Number of pages	16
Journal	Nature Metabolism
Volume	7
Issue number	8
DOIs	https://doi.org/10.1038/s42255-025-01330-w
Publication status	Published - 25 Jul 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism
Physiology (medical)
Cell Biology

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Cite this

Kunkemoeller, B., Prendeville, H., McIntyre, C., Temesgen, A., Loftus, R. M., Yao, C., Dyck, L., Sinclair, L. V., Rollings, C., Douglas, A., Pernes, G., Mitchelson, K. A. J., Harmon, C., Raverdeau, M., Ward, R., Kane, H., Kline, J., O’Brien, K. L., Brennan, M., ... Lynch, L. (2025). The source of dietary fat influences anti-tumour immunity in obese mice. Nature Metabolism, 7(8), 1630-1645. https://doi.org/10.1038/s42255-025-01330-w

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title = "The source of dietary fat influences anti-tumour immunity in obese mice",

abstract = "Obesity increases the risk of many cancers and impairs the anti-tumour immune response. However, little is known about whether the source or composition of dietary fat affects tumour growth or anti-tumour immunity in obesity. Here, we show that high-fat diets (HFDs) derived from lard, beef tallow or butter accelerate tumour growth in a syngeneic model of melanoma, but HFDs based on coconut oil, palm oil or olive oil do not, despite equivalent obesity. Using butter-based and palm oil-based HFDs as examples, we find that these dietary fat sources differentially regulate natural killer and CD8 T cell infiltration and function within the tumour microenvironment, governed by distinct effects on the plasma metabolome and intracellular metabolism. We identify diet-related lipid intermediates, namely long-chain acylcarnitine species, as immunosuppressive metabolites enriched in mice fed butter compared to palm oil HFD. Together, these results highlight the significance of diet in maintaining a healthy immune system and suggest that modifying dietary fat may improve cancer outcomes in obesity.",

author = "Britta Kunkemoeller and Hannah Prendeville and Claire McIntyre and Ayantu Temesgen and Loftus, \{Rόis{\'i}n M.\} and Conghui Yao and Lydia Dyck and Sinclair, \{Linda V.\} and Christina Rollings and Aaron Douglas and Gerard Pernes and Mitchelson, \{Kathleen A.J.\} and Cathal Harmon and Mathilde Raverdeau and Ross Ward and Harry Kane and Jaclyn Kline and O{\textquoteright}Brien, \{Katie L.\} and Martin Brennan and Frances Smith and Brenneth Stevens and Roche, \{Helen M.\} and Lavelle, \{Ed C.\} and Finlay, \{David K.\} and Cantrell, \{Doreen A.\} and Chouchani, \{Edward T.\} and Susan Kaech and Mills, \{Evanna L.\} and Marcia Haigis and Lydia Lynch",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = jul,

day = "25",

doi = "10.1038/s42255-025-01330-w",

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Kunkemoeller, B, Prendeville, H, McIntyre, C, Temesgen, A, Loftus, RM, Yao, C, Dyck, L, Sinclair, LV, Rollings, C, Douglas, A, Pernes, G, Mitchelson, KAJ, Harmon, C, Raverdeau, M, Ward, R, Kane, H, Kline, J, O’Brien, KL, Brennan, M, Smith, F, Stevens, B, Roche, HM, Lavelle, EC, Finlay, DK, Cantrell, DA, Chouchani, ET, Kaech, S, Mills, EL, Haigis, M & Lynch, L 2025, 'The source of dietary fat influences anti-tumour immunity in obese mice', Nature Metabolism, vol. 7, no. 8, pp. 1630-1645. https://doi.org/10.1038/s42255-025-01330-w

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T1 - The source of dietary fat influences anti-tumour immunity in obese mice

AU - Kunkemoeller, Britta

AU - Prendeville, Hannah

AU - McIntyre, Claire

AU - Temesgen, Ayantu

AU - Loftus, Rόisín M.

AU - Yao, Conghui

AU - Dyck, Lydia

AU - Sinclair, Linda V.

AU - Rollings, Christina

AU - Douglas, Aaron

AU - Pernes, Gerard

AU - Mitchelson, Kathleen A.J.

AU - Harmon, Cathal

AU - Raverdeau, Mathilde

AU - Ward, Ross

AU - Kane, Harry

AU - Kline, Jaclyn

AU - O’Brien, Katie L.

AU - Brennan, Martin

AU - Smith, Frances

AU - Stevens, Brenneth

AU - Roche, Helen M.

AU - Lavelle, Ed C.

AU - Finlay, David K.

AU - Cantrell, Doreen A.

AU - Chouchani, Edward T.

AU - Kaech, Susan

AU - Mills, Evanna L.

AU - Haigis, Marcia

AU - Lynch, Lydia

PY - 2025/7/25

Y1 - 2025/7/25

N2 - Obesity increases the risk of many cancers and impairs the anti-tumour immune response. However, little is known about whether the source or composition of dietary fat affects tumour growth or anti-tumour immunity in obesity. Here, we show that high-fat diets (HFDs) derived from lard, beef tallow or butter accelerate tumour growth in a syngeneic model of melanoma, but HFDs based on coconut oil, palm oil or olive oil do not, despite equivalent obesity. Using butter-based and palm oil-based HFDs as examples, we find that these dietary fat sources differentially regulate natural killer and CD8 T cell infiltration and function within the tumour microenvironment, governed by distinct effects on the plasma metabolome and intracellular metabolism. We identify diet-related lipid intermediates, namely long-chain acylcarnitine species, as immunosuppressive metabolites enriched in mice fed butter compared to palm oil HFD. Together, these results highlight the significance of diet in maintaining a healthy immune system and suggest that modifying dietary fat may improve cancer outcomes in obesity.

AB - Obesity increases the risk of many cancers and impairs the anti-tumour immune response. However, little is known about whether the source or composition of dietary fat affects tumour growth or anti-tumour immunity in obesity. Here, we show that high-fat diets (HFDs) derived from lard, beef tallow or butter accelerate tumour growth in a syngeneic model of melanoma, but HFDs based on coconut oil, palm oil or olive oil do not, despite equivalent obesity. Using butter-based and palm oil-based HFDs as examples, we find that these dietary fat sources differentially regulate natural killer and CD8 T cell infiltration and function within the tumour microenvironment, governed by distinct effects on the plasma metabolome and intracellular metabolism. We identify diet-related lipid intermediates, namely long-chain acylcarnitine species, as immunosuppressive metabolites enriched in mice fed butter compared to palm oil HFD. Together, these results highlight the significance of diet in maintaining a healthy immune system and suggest that modifying dietary fat may improve cancer outcomes in obesity.

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DO - 10.1038/s42255-025-01330-w

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EP - 1645

JO - Nature Metabolism

JF - Nature Metabolism

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ER -

The source of dietary fat influences anti-tumour immunity in obese mice

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