High-fat diet intake is associated with cardiac disorders characterised by a low-grade inflammatory process which involves NF-魏B activation. PPAR尾/未 has been proposed as a potential therapeutic target to mitigate the inflammatory process related to cardiovascular disorders. However, the involvement of this receptor in lipid-induced inflammatory response in the heart is not yet known.
The inflammatory profile was determined in hearts using mice fed with a high-fat diet (HFD) in the presence or absence of the PPAR尾/未 agonist GW501516, in hearts from knockout PPAR尾/未 mice, and in palmitate-exposed human cardiac AC16 cells in the presence or absence of GW501516 and the PPAR尾/未 antagonist GSK0660.
GW501516 treatment reduced the induction in the cardiac expression of IL-6, MCP-1 and TNF-伪, as well as the increase in DNA-binding NF-魏B activity, in mice fed the HFD. Furthermore, hearts from knockout PPAR尾/未 mice exhibited increased IL-6 and MCP-1 levels, as well as higher NF-魏B DNA-binding activity. In AC16 cells, GW501516 treatment reduced the expression of TNF-伪 and MCP-1, as well as the increase in NF-魏B DNA-binding activity caused by palmitate. GW501516 addition to these cells increased the interaction between PPAR尾/未 and the p65 subunit of NF-魏B, whereas it was prevented in the presence of the PPAR尾/未 antagonist GSK0660.
PPAR尾/未 activation reduces lipid-induced inflammation in cardiac cells through a mechanism involving the physical interaction between PPAR尾/未 and p65.