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

TY - JOUR

T1 - Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats

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

PY - 2017/2/13

Y1 - 2017/2/13

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.

U2 - 10.1371/journal.pone.0171372

DO - 10.1371/journal.pone.0171372

M3 - Journal article

SN - 1932-6203

VL - 12

JO - PLoS ONE

JF - PLoS ONE

IS - 2

ER -