{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:02:52Z","timestamp":1793898172826,"version":"4.8.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The role of saturated fatty acid-induced immunometabolic stress in macrophage dysfunction during metabolic disease remains incompletely understood, particularly the interplay between inflammatory signaling and intracellular lipid handling. We employed a tightly controlled palmitic acid (PA)-based lipotoxicity model in PMA-differentiated U937-derived human macrophage-like cells to investigate how lipid excess reshapes inflammatory responses and to evaluate the modulatory effects of cannabidiol (CBD). PA exposure induced a metabolically stressed yet viable macrophage phenotype, characterized by a broad cytokine remodeling profile. This included induction of classical proinflammatory cytokines such as interleukin (IL)-6, together with activation of inflammasome-associated cytokines IL-1\u03b2 and IL-18 and additional immunoregulatory mediators, while tumor necrosis factor alpha (TNF-\u03b1) contributed to the overall inflammatory profile in a multivariate analysis. These changes were accompanied by a significant, time-dependent storage of intracellular triglycerides (TG) consistent with lipid overload and altered lipid handling. CBD co-treatment did not compromise cell viability but selectively attenuated PA-induced inflammatory response in a cytokine-dependent manner, with the most significant reduction observed at higher concentrations. In parallel, CBD significantly reduced intracellular TG accumulation under lipotoxic conditions. Collectively, these findings define a lipotoxicity-associated macrophage phenotype driven by saturated fatty acids and identify CBD as a context-dependent modulator of immunometabolic inflammation. This work provides a controlled experimental framework to study lipid-driven inflammatory dysfunction and supports the potential of CBD as a targeted strategy to modulate metabolic inflammation without broadly suppressing immune function.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1873494","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:35:48Z","timestamp":1784216148000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Cannabidiol selectively attenuates lipotoxic immunometabolic inflammation in human macrophages"],"prefix":"10.3389","volume":"17","author":[{"given":"Mayte","family":"Rueda-Mungu\u00eda","sequence":"first","affiliation":[{"name":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud","place":["Monterrey, NL, Mexico"]},{"name":"Tecnologico de Monterrey, Institute for Obesity Research, Monterrey","place":["Monterrey, NL, 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