Palmitate drives mitochondrial and ER stress through disruption of the CD73-Adenosine axis

Bulk RNA sequencing was used to characterize transcriptional changes associated with the dysfunctional metabolic state in murine gingival fibroblasts (mGF). The mGF were treated with BSA control, palmitate, IL-1β, or palmitate plus IL-1β. Gene ontology analysis demonstrated enrichment of pathways related to innate immune activation, oxidative stress, mitochondrial dysfunction, ER stress, and purine metabolism. Palmitate disrupts the Cd73-adenosine axis while promoting mitochondrial dysfunction, oxidative stress, and Perk-mediated ER stress in gingival fibroblasts. Adenosine signaling protects against lipotoxic-induced ER stress, highlighting the relevance of the Cd73-adenosine pathway for metabolic and inflammatory diseases.