Unacylated ghrelin rapidly modulates lipogenic and insulin signaling pathway gene expression in metabolically active tissues of GHSR deleted mice.
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.
Delhanty
Patric J D
PJ
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. p.delhanty@erasmusmc.nl
Sun
Yuxiang
Y
Visser
Jenny A
JA
van Kerkwijk
Anke
A
Huisman
Martin
M
van Ijcken
Wilfred F J
WF
Swagemakers
Sigrid
S
Smith
Roy G
RG
Themmen
Axel P N
AP
van der Lely
Aart-Jan
AJ
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
D054439:Ghrelin; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin