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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. LU ; Hessner, Martin J; Jia, Shuang; Åkesson, Lina LU ; Stenlund, Hans; Moritz, Thomas; La Torre, Daria LU and Lernmark, Åke LU (2017) In PLoS ONE 12(2).
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... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
12
issue
2
publisher
Public Library of Science
external identifiers
  • scopus:85012165803
  • wos:000394423800023
ISSN
1932-6203
DOI
10.1371/journal.pone.0171372
language
English
LU publication?
yes
id
b4856ec4-7fb5-4ba4-99e3-746dd465f3fe
date added to LUP
2017-02-28 08:06:10
date last changed
2018-01-07 11:53:04
@article{b4856ec4-7fb5-4ba4-99e3-746dd465f3fe,
  abstract     = {<p>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.</p>},
  articleno    = {0171372},
  author       = {Regnell, Simon E. and Hessner, Martin J and Jia, Shuang and Åkesson, Lina and Stenlund, Hans and Moritz, Thomas and La Torre, Daria and Lernmark, Åke},
  issn         = {1932-6203},
  language     = {eng},
  month        = {02},
  number       = {2},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic BioBreeding rats},
  url          = {http://dx.doi.org/10.1371/journal.pone.0171372},
  volume       = {12},
  year         = {2017},
}