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

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

  • Free Radic Biol Med. 2024 Feb 20:212:309-321. doi: 10.1016/j.freeradbiomed.2023.12.036.
Cailong Chen 1,  Yilin Yan 2,  Yunxuan Wu 2,  Menglan Lu 3,  Yifei Xing 2,  Yujie Bai 2,  Haodong Zhao 2,  Li Ding 2,  Ying Wu 4,  Jiaying Xu 5,  Liqiang Qin 6,  Haitao Lv 7,  Zheng Zhang 8
Affiliations

Affiliations

  • 1 Center of Child Health Management, Children's Hospital of Soochow University, Suzhou, 215025, China; Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Suzhou, 215123, China.
  • 2 Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Suzhou, 215123, China.
  • 3 Suzhou Industrial Park Centers for Disease Control and Prevention, 200 Suhong West Road, Suzhou, 215021, China.
  • 4 Child Healthcare Department, Children's Hospital of Soochow University, Suzhou, 215025, China.
  • 5 State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, School of Radiation Medicine and Protection, Soochow University, 199 Renai Road, Suzhou, 215123, China.
  • 6 Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Suzhou, 215123, China. Electronic address: [email protected].
  • 7 Center of Child Health Management, Children's Hospital of Soochow University, Suzhou, 215025, China. Electronic address: [email protected].
  • 8 Center of Child Health Management, Children's Hospital of Soochow University, Suzhou, 215025, China. Electronic address: [email protected].
PMID: 38159893 DOI: 10.1016/j.freeradbiomed.2023.12.036
Abstract

Vascular endothelial dysfunction (ED) is one of the mechanisms underlying obesity-related hypertension. Perivascular adipose tissue (PVAT) surrounds blood vessels and influences the vascular endothelium function. Previous studies have demonstrated the antihypertensive effects of lactoferrin (LF) and its hydrolysates through various mechanisms. However, the effect of LF on ED and PVAT has not yet been investigated. 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.

Keywords

Endothelial dysfunction; High-fat diet; IL-18; Lactoferrin; Nitric oxide.

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