title: Next generation sequencing of sex-specific genes in the livers of obese ZSF1 rats.
abstract: 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.
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 83391 Bratislava, Slovak Republic.
authors.forename: Andrea
authors.initials: A
authors.lastname: Babelova
authors.affiliation: Institute for Systemic Physiology and Pathophysiology, University Medical Center Goettingen, 37073 Goettingen, Germany.
authors.forename: Birgitta C
authors.initials: BC
authors.lastname: Burckhardt
authors.affiliation: Department of Developmental Biochemistry, DNA Microarray and Deep-Sequencing Facility, University Medical Center Goettingen, 37077 Goettingen, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Salinas-Riester
authors.affiliation: Department of Developmental Biochemistry, DNA Microarray and Deep-Sequencing Facility, University Medical Center Goettingen, 37077 Goettingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pommerenke
authors.affiliation: Institute for Systemic Physiology and Pathophysiology, University Medical Center Goettingen, 37073 Goettingen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Burckhardt
authors.affiliation: Institute for Systemic Physiology and Pathophysiology, University Medical Center Goettingen, 37073 Goettingen, Germany. Electronic address: maja.henjakovic@med.uni-goettingen.de.
authors.forename: Maja
authors.initials: M
authors.lastname: Henjakovic
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011924:Rats, Zucker
keywords: Generation F1); Hepatic gene expression; SHHF (spontaneously hypertensive heart failure); Sex-differences; Type 2 diabetes; ZDF (Zucker diabetic fatty); ZSF1 (ZDFxSHHF-hybrid