The long noncoding RNA Bsr in the genomically imprinted DLK1-DIO3 region is suppressed in newborn rat pancreas by gestational obesity

Caroline Jaksch, Peter Grevsen Thams, Isabela Iessi, Steen Seier Poulsen, Barry Levin, Jens Høiriis Nielsen, Louise Torp Dalgaard

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.
Original languageEnglish
JournalNon-Coding RNAs in Endocrinology
Volume2018
Issue number3
Pages (from-to)5-17
Number of pages13
ISSN2300-4258
DOIs
Publication statusPublished - 2018

Cite this

Jaksch, Caroline ; Thams, Peter Grevsen ; Iessi, Isabela ; Poulsen, Steen Seier ; Levin, Barry ; Nielsen, Jens Høiriis ; Dalgaard, Louise Torp. / The long noncoding RNA Bsr in the genomically imprinted DLK1-DIO3 region is suppressed in newborn rat pancreas by gestational obesity. In: Non-Coding RNAs in Endocrinology. 2018 ; Vol. 2018, No. 3. pp. 5-17.
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title = "The long noncoding RNA Bsr in the genomically imprinted DLK1-DIO3 region is suppressed in newborn rat pancreas by gestational obesity",
abstract = "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.",
author = "Caroline Jaksch and Thams, {Peter Grevsen} and Isabela Iessi and Poulsen, {Steen Seier} and Barry Levin and Nielsen, {Jens H{\o}iriis} and Dalgaard, {Louise Torp}",
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The long noncoding RNA Bsr in the genomically imprinted DLK1-DIO3 region is suppressed in newborn rat pancreas by gestational obesity. / Jaksch, Caroline; Thams, Peter Grevsen; Iessi, Isabela; Poulsen, Steen Seier; Levin, Barry; Nielsen, Jens Høiriis; Dalgaard, Louise Torp.

In: Non-Coding RNAs in Endocrinology, Vol. 2018, No. 3, 2018, p. 5-17.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - The long noncoding RNA Bsr in the genomically imprinted DLK1-DIO3 region is suppressed in newborn rat pancreas by gestational obesity

AU - Jaksch, Caroline

AU - Thams, Peter Grevsen

AU - Iessi, Isabela

AU - Poulsen, Steen Seier

AU - Levin, Barry

AU - Nielsen, Jens Høiriis

AU - Dalgaard, Louise Torp

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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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DO - 10.1515/micrnado-2018-0002

M3 - Journal article

VL - 2018

SP - 5

EP - 17

JO - Non-Coding RNAs in Endocrinology

JF - Non-Coding RNAs in Endocrinology

SN - 2300-4258

IS - 3

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