Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats

Simon E. Regnell; Martin J. Hessner; Shuang Jia; Lina Akesson; Hans Stenlund; Thomas Moritz; Daria La Torre; Ake Lernmark

doi:10.1371/journal.pone.0171372

Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats

Simon E. Regnell, Martin J. Hessner, Shuang Jia, Lina Akesson, Hans Stenlund, Thomas Moritz, Daria La Torre, Ake Lernmark

3 Citations (Scopus)

Abstract

Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes.

Original language	English
Journal	PLoS ONE
Volume	12
Issue number	2
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0171372
Publication status	Published - 13 Feb 2017
Externally published	Yes

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Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats. / Regnell, Simon E.; Hessner, Martin J.; Jia, Shuang et al.
In: PLoS ONE, Vol. 12, No. 2, 13.02.2017.

Research output: Contribution to journal › Journal article › Research › peer-review

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abstract = "Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes.",

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AU - Regnell, Simon E.

AU - Hessner, Martin J.

AU - Jia, Shuang

AU - Akesson, Lina

AU - Stenlund, Hans

AU - Moritz, Thomas

AU - La Torre, Daria

AU - Lernmark, Ake

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N2 - Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes.

AB - Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes.

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Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats

Abstract

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