Endocrine. 2026 Oct 31;91(1):364. doi: 10.1007/s12020-026-04838-7.
ABSTRACT
PURPOSE: Maternal high-fat diet (HFD) exposure induces sex-dependent cardiac hypertrophy in adult offspring, but the underlying mechanisms remain unclear. This study investigated the role of miR-493-3p in maternal HFD-induced cardiac hypertrophy and its potential association with estrogen regulation and PI3K/AKT/mTOR signaling.
METHODS: Pregnant rats were fed either a standard chow diet or HFD (60% kcal fat). Hearts from adult offspring were analyzed by miRNA sequencing, real-time RT-PCR, and western blotting. Ovariectomy (OVX) and sham operations were performed in adult female offspring. Neonatal rat cardiomyocytes (NRCMs) were treated with estrogen or transfected with miR-493-3p mimic or inhibitor, with or without angiotensin II (Ang II) stimulation.
RESULTS: miR-493-3p was the most markedly upregulated miRNA in the hearts of HFD-exposed male offspring. Maternal HFD increased cardiac miR-493-3p expression in adult males but decreased it in females. OVX increased cardiac miR-493-3p expression in female offspring, and HFD combined with OVX further enhanced this increase. Consistently, estrogen suppressed miR-493-3p expression in NRCMs. miR-493-3p overexpression increased cardiomyocyte surface area, upregulated Nppa and Myh7, and reduced Myh6, whereas miR-493-3p inhibition attenuated Ang II-induced hypertrophic responses. KEGG analysis indicated enrichment of predicted miR-493-3p targets in the PI3K/AKT pathway. Maternal HFD also increased PI3K p85, PI3K p110, p-AKT, and p-mTOR protein expression in adult male offspring, but decreased p-AKT/AKT and p-mTOR/mTOR in adult female offspring.
CONCLUSION: Maternal HFD-induced miR-493-3p upregulation may promote cardiac hypertrophy through PI3K/AKT/mTOR activation, whereas estrogen-mediated suppression of miR-493-3p may contribute to protection in female offspring.
PMID:42965768 | DOI:10.1007/s12020-026-04838-7