Volume 5, Issue 3 (2025) – 4 articles
Cover Picture: Chronic exposure to an obesogenic diet (OBD) disrupts lipid-immune homeostasis and promotes inflammation, but its reversibility during aging remains unclear. This study investigated whether switching OBD-fed mice to a control diet could restore immune-lipid balance and improve post-myocardial infarction responses. Chronic OBD caused cardiac dysfunction, expansion of CCR2+ macrophages, elevated 12-HETE, and depletion of specialized pro-resolving mediators (SPMs). Dietary reversal restored SPMs and some immune parameters, yet persistent activation of the 12-HETE-induced CCL2-CCR2/ALOX5-ALOX5AP axis maintained proinflammatory macrophage memory. Single-cell RNA sequencing revealed diet-dependent transcriptional remodeling of immune populations, and LPS stimulation confirmed enhanced inflammatory memory in macrophages. These findings indicate that dietary intervention can mitigate OBD-induced inflammation during aging, with the 12-HETE-induced axis playing a central role in sustaining inflammatory immune memory.
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