1177-P: Maternal Insulin Intervention Improves Offspring Glucose Metabolism via Long Noncoding RNA

Abstract

Maternal high fat (HF) during pregnancy is known to have numerous adverse effects on offspring, including increased adiposity and impaired glucose tolerance later in life. The aim of this study was to determine if prebiotic early intervention could mitigate some of the negative effects of maternal HF and involved mechanism. C57BL mice were fed a HF diet, normal diet or a HF diet with prebiotic supplementation during pregnancy and lactation. At 8 weeks of age, glucose tolerance were measured in the offspring. And offspring livers were obtained to assay lncRNA and mRNA profiles to investigate the effects of early maternal inulin intervention on offspring. Offspring from HF-fed dams displayed glucose intolerance and an insulin resistance phenotype at 8 weeks of age. Early maternal inulin intervention improved glucose metabolism in male offspring of mothers fed a HF during gestation and lactation. The lncRNA and mRNA profile data revealed that compared with the offspring from HF dams, offspring from the early inulin intervention dams had 99 differentially expressed hepatic lncRNAs and 529 differentially expressed mRNAs. The differentially expressed lncRNA-mRNA coexpression analysis demonstrated that early maternal inulin intervention may change hepatic lncRNA expression in offspring. These lncRNAs are involved in metabolic pathways and the AMP-activated protein kinase signaling pathway. Importantly, the early maternal inulin intervention alleviated glucose metabolism by inhibiting the lncRNA Serpina4-ps1/let-7b-5p/Ppargc1a as a competing endogenous RNA in male offspring. Disclosure Q.Zhang: None. X.Xiao: None. M.Li: None. Funding National Natural Science Foundation of China (82170854, 81870579, 81870545, 81570715, 81170736); Beijing Natural Science Foundation (7202163); Beijing Municipal Science & Technology Commission (Z201100005520011); National High Level Hospital Clinical Research Funding (2022-PUMCH-C-019); National Key Research and Development Program of China (2018YFC2001100); CAMS Innovation Fund for Medical Sciences (CIFMS2021-1-I2M-002, CIFMS2017-I2M-1-008)