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

Genomics. 2015 Oct;106(4):204-13. doi: 10.1016/j.ygeno.2015.07.006. Epub 2015 Jul 19.


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.

Keywords: Generation F1); Hepatic gene expression; SHHF (spontaneously hypertensive heart failure); Sex-differences; Type 2 diabetes; ZDF (Zucker diabetic fatty); ZSF1 (ZDFxSHHF-hybrid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / genetics*
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation
  • High-Throughput Nucleotide Sequencing / methods*
  • Liver / metabolism
  • Male
  • Rats
  • Rats, Zucker