Omega-3 PUFAs reduce inflammation by targeting NRF2 and NF-κB activity in an ex vivo model of cardiac mature adipocytes and adipose derived stem cells from atherosclerotic patients

< 0.05). This downregulation was accompanied by increased expression of uncoupling proteins (UCP)1 and 2 and heme-oxygenase (HO)-1 and of the anti-inflammatory and pro-resolving lipid mediator resolvin D1. Mechanistically, this protective modulation appears to be driven by the upregulation of peroxisome proliferator-activated receptor gamma (PPAR)-γ and nuclear factor erythroid 2-related factor (NRF)2, leading to increased NRF2 activity and suppressed NF-κB signaling. Functionally, supernatants from DHA-conditioned adipocytes exhibited reduced monocyte-attracting activity in chemotaxis assays. While EPA conditioning produced effects similar to DHA, arachidonic acid (AA) showed no significant biological effects. In conclusion, DHA and EPA mitigated the PAT inflammatory profile, highlighting the potential therapeutic role of such PUFAs in reducing cardiac adipose tissue inflammation. These results may have implications for treatment of CAD patients.