Transcriptomic evidence of hypothalamus for maternal fructose exposure induced offspring hypertension through AT1R/TLR4 pathway

Abstract

Maternal fructose exposure during pregnancy and lactation has been shown to contribute to hypertension in offspring, with long-term effects on hypothalamus development. However, the underlying mechanisms remain unclear. In this study, we used the tail-cuff method to evaluate the effects of maternal fructose drinking exposure on offspring blood pressure levels at postpartum day 21 (PND21) and postpartum day 60 (PND60). We employed Oxford Nanopore Technologies (ONT) full-length RNA sequencing to investigate the developmental programming of the PND60 offspring's hypothalamus and confirmed the presence of the AT1R/TLR4 pathway using western blot and immunofluorescence. Our findings demonstrated that maternal fructose exposure significantly increased blood pressure in PND60 offspring but not in PND21 offspring. Additionally, we observed transcriptome-wide alterations in the hypothalamus of PND60 offspring following maternal fructose exposure. Overall, our study provides evidence that maternal fructose exposure during pregnancy and lactation may alter the transcriptome-wide of offspring hypothalamus and activate the AT1R/TLR4 pathway, leading to hypertension. These findings may have important implications for the prevention and treatment of hypertension-related diseases in offspring exposed to excessive fructose during pregnancy and lactation.