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,Åke Lernmark,Lina Åkesson,Martin J Hessner,Shuang Jia,Thomas Moritz,Daria La Torre,Hans Stenlund

doi:10.1371/journal.pone.0171372

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.

Highlights

Type 1 diabetes is characterized by the autoimmune destruction of the pancreatic beta cells, causing a deficiency of insulin
We found that hepatic gene expression relating to lipid metabolism was significantly changed following disease onset and that there was a significant overlap with genes regulated by insulin
Patients with type 1 diabetes have abnormal lipoprotein patterns, even if they have optimal glycemic control [34]. Based on these findings, which are unrelated to diabetes duration, we expected hepatic lipid metabolism to change during the transition from normoglycemia to hyperglycemia in BBDR.lyp/lyp rats

Summary

Introduction

Type 1 diabetes is characterized by the autoimmune destruction of the pancreatic beta cells, causing a deficiency of insulin. Long before the appearance of autoantibodies, differences in the serum levels of certain lipids can be measured in persons who go on to develop type 1 diabetes compared to controls. These differences appear to exist already in utero, as umbilical cord blood levels of phosphatidylcholines and phosphatidylethanolamines were significantly decreased in children diagnosed with type 1 diabetes before 4. Hepatic transcriptome and serum metabolome in BB rats by National Institutes of Health grant R01AI078713 and The Children’s Hospital of Wisconsin Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Methods

Results

Discussion

Conclusion