Next generation sequencing of sex-specific genes in the livers of obese ZSF1 rats

• We investigated gene expression in livers of ZSF1 (ZDFxSHHF-hybrid, generation F1) rats for the first time.
• We have identified 103 sex-dependently expressed genes in livers of obese ZSF1 rats using next-generation sequencing (NGS).
• Identified sex-differently genes are involved in the detoxification, metabolism, and secretion of, e.g. drugs.
• The sex-differently expression of Cyp2c11, Cyp4a2, Gstm2, and Oat3 may have an impact on drug handling in type 2 diabetes.

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.