Quick Study Analysis: Seed Oils Promote Leukemia?

tldr: The active leukemia-promoting ingredient of a famous HFD is linoleic acid, the primary fat in seed oils.

Obesity is associated with leukemia, apparently.

These scientists wanted to figure out how the most commonly-used high-fat diet (D12492, of course) promotes leukemia, since it also promotes obesity.

See my post below about how for more—a lot more.

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Of course, we know that what promotes obesity in D12492 is the linoleic acid.

“Weight measurement of WT and PRKI mice after the initiation of SD or HFD. Weight gain was identical in both strains.” (Mazzarella et al., 2024, Figure 1A)

Turns out that's not all it does!

A high-linoleic diet significantly increases death from leukemia. (Mazzarella et al., 2024, Figure 1B)

From an editorial describing the research:

"From risk association between acute promyelocytic leukemia (APL) and obese-overweight individuals, Mazzarella and colleagues hypothesized that a high-fat diet (HFD) promotes development of APL.

"Using mouse APL model (PML-RARα knock-in), the authors demonstrated that linoleic acid drives activation of PPARδ in hematopoietic progenitors, and that activation of PPARδ increases proliferation of progenitor cells with PML-RARA expression toward APL.

“...while suggesting use of diet rich in linoleic acid with caution." (Yamada and Rao, 2024)

Mazzarella et al., (2024) note that:

"In this study we provide mechanistic evidence that obesity directly promotes APL leukemogenesis through a PPARδ/PMLRARα transcriptional circuit that is activated by PUFA and in particular [Linoleic Acid: LA]."

Concluding:

“Furthermore, we identify LA and probably PUFAs in general as a major target for intervention. LA is the most highly consumed fatty acid in Western diets; maintaining an adequate ratio of mono-vs poly-unsaturated fatty acids is already a mainstay of several nutritional guidelines, mostly based on epidemiological evidence correlating a high poly- vs mono-unsaturated fats with poor cardiovascular risk.”

These authors note that they are recapitulating prior work:

“Both LA and PPARδ have been previously and independently shown to play a role in normal and cancer SC self-renewal, both in hematopoietic stem cells and epithelial tumors like colorectal cancer.”

The colorectal cancer paper is (Beyaz et al., 2016), which also uses D12492.

The average person eating a Western, industrial diet eats vastly more LA than is found in a healthy diet. Act accordingly.

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References

Beyaz, S., Mana, M. D., Roper, J., Kedrin, D., Saadatpour, A., Hong, S.-J., Bauer-Rowe, K. E., Xifaras, M. E., Akkad, A., Arias, E., Pinello, L., Katz, Y., Shinagare, S., Abu-Remaileh, M., Mihaylova, M. M., Lamming, D. W., Dogum, R., Guo, G., Bell, G. W., … Yilmaz, Ö. H. (2016). High fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature, 531(7592), 53–58. https://doi.org/10.1038/nature17173

Mazzarella, L., Falvo, P., Adinolfi, M., Tini, G., Gatti, E., Piccioni, R., Bonetti, E., Gavilán, E., Valli, D., Gruszka, A., Bodini, M., Gallo, B., Orecchioni, S., de Michele, G., Migliaccio, E., Duso, B. A., Roerink, S., Stratton, M., Bertolini, F., … Pelicci, P. G. (2024). High-Fat Diet Promotes Acute Promyelocytic Leukemia through PPARδ-Enhanced Self-renewal of Preleukemic Progenitors. Cancer Prevention Research, 17(2), 59–75. https://doi.org/10.1158/1940-6207.CAPR-23-0246 BioRxiv link to pre-publication version used here: https://www.biorxiv.org/content/10.1101/2022.03.14.483944v1.full

Research Diets, Inc. (2006). D12492 Formula [Advertisement]. Research Diets, Inc.: D12492: Rodent Diet With 60 Kcal% Fat. https://researchdiets.com/formulas/d12492

Yamada, H. Y., & Rao, C. V. (2024). High-Fat Diet Induced PPARδ Promotes Self-renewal of Preleukemic Progenitors in Development of Acute Promyelocytic Leukemia. Cancer Prevention Research, 17(2), 47–49. https://doi.org/10.1158/1940-6207.CAPR-23-0469