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  • Title: Maternal obesity alters circRNA expression and the potential role of mmu_circRNA_0000660 via sponging miR_693 in offspring liver at weaning age.
    Author: Chen Q, Liu M, Luo Y, Yu H, Zhang J, Li D, He Q.
    Journal: Gene; 2020 Mar 20; 731():144354. PubMed ID: 31935513.
    Abstract:
    BACKGROUND AND AIMS: Maternal obesity predispose offspring to metabolic disorders and obesity, but the mechanisms are not fully understood, especially during early life. Circular RNA (circRNA) can regulate the expression of target genes through the regulatory pathways of competing endogenous RNA (ceRNA). We hypothesized that the offspring of obese dams exhibit impaired metabolic health through the dysregulated expression of hepatic circRNA. METHODS AND RESULTS: A high-fat diet (HFD) or standard chow diet (CD) were randomized to dams for 12 weeks before mating. Specific diets continued for each dam throughout pregnancy and lactation. Then, lipid metabolic parameters were assessed in dams and female offspring. We performed liver RNA sequencing (RNA-seq) for the offspring of HFD- and CD-dams to comprehensively identify differentially expressed (DE) circRNA and messenger RNA (mRNA). Further, ceRNA networks combining DE circRNA, mRNA, and microRNA were predicted based on MiRanda and TargetScan databases combined with the lipid metabolism-related pathway. As a result, the circRNA_0000660-miR_693-Igfbp1 regulatory pathway was selected from liver and AML12 cell line. Quantitative real-time polymerase chain reaction, dual luciferase reporter gene system, and Small interfering RNA for circRNA_0000660 transfection experiment were applied to validate. CONCLUSIONS: Our work investigated new mechanisms of the effect of maternal obesity on offspring's lipid metabolism. Several novel targets were uncovered to reverse the effect.
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