title: The transcriptomic signature of fasting murine liver.
abstract: BACKGROUND
  The contribution of individual organs to the whole-body adaptive response to fasting has not been established. Hence, gene-expression profiling, pathway, network and gene-set enrichment analysis and immunohistochemistry were carried out on mouse liver after 0, 12, 24 and 72 hours of fasting.
  
  
  RESULTS
  Liver wet weight had declined approximately 44, approximately 5, approximately 11 and approximately 10% per day after 12, 24, 48 and 72 hours of fasting, respectively. Liver structure and metabolic zonation were preserved. Supervised hierarchical clustering showed separation between the fed, 12-24 h-fasted and 72 h-fasted conditions. Expression profiling and pathway analysis revealed that genes involved in amino-acid, lipid, carbohydrate and energy metabolism responded most significantly to fasting, that the response peaked at 24 hours, and had largely abated by 72 hours. The strong induction of the urea cycle, in combination with increased expression of enzymes of the tricarboxylic-acid cycle and oxidative phosphorylation, indicated a strong stimulation of amino-acid oxidation peaking at 24 hours. At this time point, fatty-acid oxidation and ketone-body formation were also induced. The induction of genes involved in the unfolded-protein response underscored the cell stress due to enhanced energy metabolism. The continuous high expression of enzymes of the urea cycle, malate-aspartate shuttle, and the gluconeogenic enzyme Pepck and the re-appearance of glycogen in the pericentral hepatocytes indicate that amino-acid oxidation yields to glucose and glycogen synthesis during prolonged fasting.
  
  
  CONCLUSIONS
  The changes in liver gene expression during fasting indicate that, in the mouse, energy production predominates during early fasting and that glucose production and glycogen synthesis become predominant during prolonged fasting.
authors.affiliation: AMC Liver Center, Academic Medical Center, University of Amsterdam, The Netherlands. m.sokolovic@amc.uva.nl
authors.forename: Milka
authors.initials: M
authors.lastname: Sokolović
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Sokolović
authors.forename: Diederik
authors.initials: D
authors.lastname: Wehkamp
authors.forename: Emiel
authors.initials: E
authors.lastname: Ver Loren van Themaat
authors.forename: Dirk R
authors.initials: DR
authors.lastname: de Waart
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Gilhuijs-Pederson
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nikolsky
authors.forename: Antoine H C
authors.initials: AH
authors.lastname: van Kampen
authors.forename: Theodorus B M
authors.initials: TB
authors.lastname: Hakvoort
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Lamers
mesh_terms: D000818:Animals; D050260:Carbohydrate Metabolism / Q000235:genetics; D005215:Fasting / Q000502:physiology*; D005508:Food Deprivation / Q000502:physiology; D015870:Gene Expression; D020869:Gene Expression Profiling; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress
chemical_list: D008112:Liver Glycogen