title: Sex-different hepaticglycogen content and glucose output in rats.
abstract: BACKGROUND
  Genes involved in hepatic metabolism have a sex-different expression in rodents. To test whether male and female rat livers differ regarding lipid and carbohydrate metabolism, whole-genome transcript profiles were generated and these were complemented by measurements of hepatic lipid and glycogen content, fatty acid (FA) oxidation rates and hepatic glucose output (HGO). The latter was determined in perfusates from in situ perfusion of male and female rat livers. These perfusates were also analysed using nuclear magnetic resonance (NMR) spectroscopy to identify putative sex-differences in other liver-derived metabolites. Effects of insulin were monitored by analysis of Akt-phosphorylation, gene expression and HGO after s.c. insulin injections.
  
  
  RESULTS
  Out of approximately 3 500 gene products being detected in liver, 11% were significantly higher in females, and 11% were higher in males. Many transcripts for the production of triglycerides (TG), cholesterol and VLDL particles were female-predominant, whereas genes for FA oxidation, gluconeogenesis and glycogen synthesis were male-predominant. Sex-differences in mRNA levels related to metabolism were more pronounced during mild starvation (12 h fasting), as compared to the postabsorptive state (4 h fasting). No sex-differences were observed regarding hepatic TG content, FA oxidation rates or blood levels of ketone bodies or glucose. However, males had higher hepatic glycogen content and higher HGO, as well as higher ratios of insulin to glucagon levels. Based on NMR spectroscopy, liver-derived lactate was also higher in males. HGO was inhibited by insulin in parallel with increased phosphorylation of Akt, without any sex-differences in insulin sensitivity. However, the degree of Thr172-phosphorylated AMP kinase (AMPK) was higher in females, indicating a higher degree of AMPK-dependent actions.
  
  
  CONCLUSIONS
  Taken together, males had higher ratios of insulin to glucagon levels, higher levels of glycogen, lower degree of AMPK phosphorylation, higher expression of gluconeogenic genes and higher hepatic glucose output. Possibly these sex-differences reflect a higher ability for the healthy male rat liver to respond to increased energy demands.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Sweden.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gustavsson
authors.forename: Kamal
authors.initials: K
authors.lastname: Yassin
authors.forename: Erik
authors.initials: E
authors.lastname: Wahlström
authors.forename: Louisa
authors.initials: L
authors.lastname: Cheung
authors.forename: Johan
authors.initials: J
authors.lastname: Lindberg
authors.forename: Kerstin
authors.initials: K
authors.lastname: Brismar
authors.forename: Claes-Göran
authors.initials: CG
authors.lastname: Ostenson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Norstedt
authors.forename: Petra
authors.initials: P
authors.lastname: Tollet-Egnell
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D001786:Blood Glucose / Q000032:analysis* / Q000235:genetics; D005215:Fasting; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006003:Glycogen / Q000032:analysis* / Q000097:blood / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D014280:Triglycerides / Q000032:analysis / Q000097:blood
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D014280:Triglycerides; D006003:Glycogen; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases