Saturated fatty acid chain length shapes B cell lymphoma metabolism and progression
- 1Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montreal, Canada , Department of Obstetrics-Gynecology, Université de Montréal, Montreal, Canada., Centr
Abstract
B-cell lymphomas reprogram cellular metabolism to sustain their rapid growth and proliferation. Despite their close proximity to adipose tissue and the paradoxical association between obesity and improved lymphoma outcomes, how fatty-acid availability and dietary fat composition influence B-cell lymphoma remains poorly understood. Importantly, saturated fatty acids of different chain lengths have distinct routes of cellular uptake and metabolic fates and may therefore exert divergent effects on tumour growth. Here, we investigated how medium-chain and long-chain saturated fatty acids, their dietary availability, and their transfer from adipocytes shape B-cell lymphoma metabolism and progression. We found that B-cell lymphoma cells were dependent on fatty-acid uptake, activation, and utilization for proliferation. Additionally, we identified adipocytes as microenvironmental players that transfer fatty acids and suppress cell growth. Interestingly, in most B-cell lymphomas, exogenous palmitate limits lymphoma cell proliferation, while MCFA caprylic acid showed only mild effects. Using a syngeneic B-cell lymphoma orthotopic model, we found that an MCFA-rich diet increased lymphoma burden and accelerated lymph-node progression, whereas LCFA-rich and obesogenic diets restricted lymphoma dissemination. Dietary fatty-acid composition also altered T-cell exhaustion and profoundly remodelled the circulating lipidome, with LCFA-rich and obesogenic diets producing highly concordant lipidomic signatures distinct from MCFA feeding. Across B-cell lymphoma cell lines, low ACSL1 expression was associated with increased palmitate sensitivity, which we computationally modelled as a targetable vulnerability in B-cell lymphoma treatment. Taken together, our results show that lipid metabolism is a metabolic vulnerability that can be targeted through dietary intervention.
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BibTeX
@misc{collin2026saturated,
title = {{Saturated fatty acid chain length shapes B cell lymphoma metabolism and progression}},
author = {A. L. Collin and M. Pyun and L. Bourguignon and B. B. Ngwenyama and M. Laflamme and C. Giambagno and E. B. Gianneli and I. Giacomini and A. Malina and E. C. Cheung and F. Zani and M. Craig and J. Blagih},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.18.752627},
url = {https://www.biorxiv.org/content/10.64898/2026.09.18.752627v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Saturated fatty acid chain length shapes B cell lymphoma metabolism and progression
AU - A. L. Collin
AU - M. Pyun
AU - L. Bourguignon
AU - B. B. Ngwenyama
AU - M. Laflamme
AU - C. Giambagno
AU - E. B. Gianneli
AU - I. Giacomini
AU - A. Malina
AU - E. C. Cheung
AU - F. Zani
AU - M. Craig
AU - J. Blagih
PY - 2026
DA - 2026/09/18
PB - bioRxiv
DO - 10.64898/2026.09.18.752627
UR - https://www.biorxiv.org/content/10.64898/2026.09.18.752627v1
AB - B-cell lymphomas reprogram cellular metabolism to sustain their rapid growth and proliferation. Despite their close proximity to adipose tissue and the paradoxical association between obesity and improved lymphoma outcomes, how fatty-acid availability and dietary fat composition influence B-cell lymphoma remains poorly understood. Importantly, saturated fatty acids of different chain lengths have distinct routes of cellular uptake and metabolic fates and may therefore exert divergent effects on tumour growth. Here, we investigated how medium-chain and long-chain saturated fatty acids, their dietary availability, and their transfer from adipocytes shape B-cell lymphoma metabolism and progression. We found that B-cell lymphoma cells were dependent on fatty-acid uptake, activation, and utilization for proliferation. Additionally, we identified adipocytes as microenvironmental players that transfer fatty acids and suppress cell growth. Interestingly, in most B-cell lymphomas, exogenous palmitate limits lymphoma cell proliferation, while MCFA caprylic acid showed only mild effects. Using a syngeneic B-cell lymphoma orthotopic model, we found that an MCFA-rich diet increased lymphoma burden and accelerated lymph-node progression, whereas LCFA-rich and obesogenic diets restricted lymphoma dissemination. Dietary fatty-acid composition also altered T-cell exhaustion and profoundly remodelled the circulating lipidome, with LCFA-rich and obesogenic diets producing highly concordant lipidomic signatures distinct from MCFA feeding. Across B-cell lymphoma cell lines, low ACSL1 expression was associated with increased palmitate sensitivity, which we computationally modelled as a targetable vulnerability in B-cell lymphoma treatment. Taken together, our results show that lipid metabolism is a metabolic vulnerability that can be targeted through dietary intervention.
ER -