title: Unacylated ghrelin rapidly modulates lipogenic and insulin signaling pathway gene expression in metabolically active tissues of GHSR deleted mice.
abstract: BACKGROUND
  There is increasing evidence that unacylated ghrelin (UAG) improves insulin sensitivity and glucose homeostasis; however, the mechanism for this activity is not fully understood since a UAG receptor has not been discovered.
  
  
  RESULTS
  To assess potential mechanisms of UAG action in vivo, we examined rapid effects of UAG on genome-wide expression patterns in fat, muscle and liver of growth hormone secretagogue receptor (GHSR)-ablated mice using microarrays. Expression data were analyzed using Ingenuity Pathways Analysis and Gene Set Enrichment Analysis. Regulation of subsets of these genes was verified by quantitative PCR in an independent experiment. UAG acutely regulated clusters of genes involved in glucose and lipid metabolism in all three tissues, consistent with enhancement of insulin sensitivity.
  
  
  CONCLUSIONS
  Fat, muscle and liver are central to the control of lipid and glucose homeostasis. UAG rapidly modulates the expression of metabolically important genes in these tissues in GHSR-deleted mice indicating a direct, GHSR-independent, action of UAG to improve insulin sensitivity and metabolic profile.
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. p.delhanty@erasmusmc.nl
authors.forename: Patric J D
authors.initials: PJ
authors.lastname: Delhanty
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Sun
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Visser
authors.forename: Anke
authors.initials: A
authors.lastname: van Kerkwijk
authors.forename: Martin
authors.initials: M
authors.lastname: Huisman
authors.forename: Wilfred F J
authors.initials: WF
authors.lastname: van Ijcken
authors.forename: Sigrid
authors.initials: S
authors.lastname: Swagemakers
authors.forename: Roy G
authors.initials: RG
authors.lastname: Smith
authors.forename: Axel P N
authors.initials: AP
authors.lastname: Themmen
authors.forename: Aart-Jan
authors.initials: AJ
authors.lastname: van der Lely
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D005260:Female; D054439:Ghrelin / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology; D054440:Receptors, Ghrelin / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D054439:Ghrelin; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin