Restoration of vascular dysfunction resulting from maternal high-fat diet via modulation of the NLRP3/IL-1β axis

Clin Exp Hypertens. 2025 Dec;47(1):2440342. doi: 10.1080/10641963.2024.2440342. Epub 2024 Dec 26.

Abstract

This study investigated the impact of maternal high-fat diet on vascular function and endothelial homeostasis in offspring. We found that offspring exposed to maternal high-fat diet exhibited elevated blood pressure, impaired abdominal aortic vascular function, and endothelial homeostasis imbalance. These changes were accompanied by increased levels of reactive oxygen species (ROS) and upregulation of pro-inflammatory cytokines (including IL-1β, TNF-α, IL-6, and IL-10). Treatment with NLRP3 or IL-1β inhibitors prevented the deterioration in vascular function, reduced endothelial NO production, and inflammation induced by maternal high-fat diet exposure compared to the control group. The findings suggest that during pregnancy, mitigating the vascular impairments in offspring induced by maternal high-fat diet can be achieved by inhibiting the NLRP3/IL-1β pathway.

Keywords: Maternal obesity; endothelial homeostasis; fetal programming; hypertension; vascular function.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Diet, High-Fat* / adverse effects
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Female
  • Interleukin-1beta* / metabolism
  • Male
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism
  • Prenatal Exposure Delayed Effects / physiopathology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Interleukin-1beta
  • Reactive Oxygen Species
  • Nlrp3 protein, mouse