Journal
GENOMICS
Volume 106, Issue 4, Pages 204-213Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2015.07.006
Keywords
Type 2 diabetes; Hepatic gene expression; Sex-differences; ZSF1 (ZDFxSHHF-hybrid Generation F1); ZDF (Zucker diabetic fatty); SHHF (spontaneously hypertensive heart failure)
Funding
- Deutsche Forschungsgemeinschaft (DFG
- German Research Foundation) [HE 6926/1-1]
- University Medical Center Goettingen
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Type 2 diabetes induces pathophysiological changes in the liver. The aim of this study was to identify differently expressed genes in the livers of male and female ZSF1 rats (ZDFxSHHF-hybrid, generation F1), a model for type 2 diabetes. Gene expression was investigated using next-generation sequencing (NGS). Selected candidate genes were verified by real-time PCR in the livers of obese and lean rats. 103 sex-different genes, associated to pathways response to chemical stimulus, lipid metabolism, and response to organic substance, were identified. Male-specific genes were involved in hepatic metabolism, detoxification, and secretion, e.g. cytochrome P450 2c11 (Cyp2c11), Cyp4a2, glutathione S-transferases mu 2 (Gstm2), and Slc22a8 (organic anion transporter 3, Oat3). Most female-specific genes were associated to lipid metabolism (e.g. glycerol-3-phosphate acyltransferase 1, Gpam) or glycolysis (e.g. glucokinase, Gck). Our data suggest the necessity to pay attention to sex- and diabetes-dependent changes in pre-clinical testing of hepatic metabolized and secreted drugs. (C) 2015 Published by Elsevier Inc.
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