Abstract

Abstract Background: Fetal metabolic programming imposed by maternal obesity and impaired glucose tolerance predisposes the offspring to metabolic disease and beta cell dysfunction as adults. The aim of this study was to assess the whole pancreas RNA changes in neonatal offspring exposed to fetal programming. Methods: The outcome of fetal programming on offspring was tested using the selectively bred Diet Induced Obese (DIO) and the Diet Resistant (DR) strains. DIO and DR rats were fed either chow or high fat, high sucrose (high energy, HE) diet during gestation and the differences in pancreas RNA expression at two days after birth were measured by microarray. Pancreas sections were stained and analyzed for alpha and beta cell numbers. Neonatal islets were treated with cytotoxic cytokines and RNA measured by RT-Q-PCR. Results: Morphometric analyses revealed significant differences in alpha and beta cell numbers per pancreas or per islet by HE diet. Microarray analyses revealed 11 fold downregulation of the long noncoding RNA Bsr in whole pancreas by HE feeding of DIO rat dams. MicroRNAs from the same locus, the Dlk1- Dio3 imprinted region, were also decreased by HE diet. Moreover, treatment of isolated neonatal islets with inflammatory cytokines, IL-1β and IFN-γ, led to reduction of Bsr transcript in a time and dose dependent manner. Conclusions: Our data suggest that fetal programming of Bsr may play a role in beta cell dysfunction in obesity and type 2 diabetes.

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