Prenatal High-Sucrose Diet Induced Vascular Dysfunction of Renal Interlobar Arteries in the Offspring via PPARγ-RXRg-ROS/Akt Signaling

Mol Nutr Food Res. 2024 May;68(10):e2300871. doi: 10.1002/mnfr.202300871. Epub 2024 May 5.

Abstract

Scope: Prenatal nutrition imbalance correlates with developmental origin of cardiovascular diseases; however whether maternal high-sucrose diet (HS) during pregnancy causes vascular damage in renal interlobar arteries (RIA) from offspring still keeps unclear.

Methods and results: Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Swollen mitochondria and distributed myofilaments are observed in vascular smooth muscle cells of RIA exposed to prenatal HS. Maternal HS increases phenylephrine (PE)-induced vasoconstriction in the RIA from adult offspring. NG-Nitro-l-arginine (L-Name) causes obvious vascular tension in response to PE in offspring from control group, not in HS. RNA-Seq of RIA is performed to reveal that the gene retinoid X receptor g (RXRg) is significantly decreased in the HS group, which could affect vascular function via interacting with PPARγ pathway. By preincubation of RIA with apocynin (NADPH inhibitor) or capivasertib (Akt inhibitor), the results indicate that ROS and Akt are the vital important factors to affect the vascular function of RIA exposure to prenatal HS.

Conclusion: Maternal HS during the pregnancy increases PE-mediated vasoconstriction of RIA from adult offspring, which is mainly related to the enhanced Akt and ROS regulated by the weakened PPARγ-RXRg.

Keywords: Akt; RIA; ROS; RRARγ; vasoconstriction.

MeSH terms

  • Animals
  • Dietary Sucrose / adverse effects
  • Female
  • Male
  • Maternal Nutritional Physiological Phenomena
  • PPAR gamma* / genetics
  • PPAR gamma* / metabolism
  • Phenylephrine / pharmacology
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Proto-Oncogene Proteins c-akt* / genetics
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Rats
  • Rats, Sprague-Dawley*
  • Reactive Oxygen Species* / metabolism
  • Renal Artery / drug effects
  • Signal Transduction* / drug effects
  • Vasoconstriction* / drug effects

Substances

  • PPAR gamma
  • Proto-Oncogene Proteins c-akt
  • Reactive Oxygen Species
  • Dietary Sucrose
  • Phenylephrine