Lactoferrin ameliorated obesity-induced endothelial dysfunction by inhibiting the Tak1/IL-18/eNOS pathway between PVAT and vascular endothelium

In this study, we examined the influence of LF on ED and PVAT using high-fat diet mice as well as MAEC cells and 3T3-L1 adipocytes. Finally, LF supplementation decreases the systolic blood pressure (SBP), serum adhesion molecule (ICAM-1 and VCAM-1), and aorta ROS levels, and improves endothelium-dependent relaxation function in high-fat diet mice. Moreover, LF supplementation down-regulates the Tak1/IL-18/eNOS pathway between PVAT and aorta and enhances the NO generation in high-fat diet mice. In addition, we observe that LF decreases the expression levels of IL-18 and p-Tak1 in 3T3-L1 adipocytes, but fails to influence the eNOS and p-eNOS expression levels in MAEC cells. Finally, the significant associations between LF and IL-18 and SBP and hypertension risk are also observed in obesity children only. These findings provide evidence that the Tak1/IL-18/eNOS pathway between the aorta and PVAT is important in obesity-related ED, and LF may improve ED or even hypertension by down-regulating this pathway.PMID:38159893 | DOI:10.1016/j.freeradbiomed.2023.12.036
Source: Free Radical Biology and Medicine - Category: Biology Authors: Source Type: research