Hypothalamic gene expression following ghrelin therapy to gastrectomized rodents.
We investigated whether ghrelin depletion (by gastrectomy surgery) and/or treatment/replacement with the gastric hormone ghrelin alters the expression of key hypothalamic genes involved in energy balance, in a manner consistent with ghrelin's pro-obesity effects. At 2 weeks after surgery mice were treated with ghrelin (12 nmol/mouse/day, sc) or vehicle for 8 weeks. Gastrectomy had little effect on the expression of these genes, with the exception of NPY mRNA in the arcuate nucleus that was increased. Ghrelin treatment (to gastrectomized and sham mice) increased the mRNA expression of orexigenic peptides NPY and AgRP while decreasing mRNA expression of the anorexigenic peptide POMC. Two weeks gavage treatment with the ghrelin mimetic, MK-0677, to rats increased NPY and POMC mRNA in the arcuate nucleus and MCH mRNA in the lateral hypothalamus. Thus, while predicted pro-obesity ghrelin signalling pathways were activated by ghrelin and ghrelin mimetics, these were largely unaffected by gastrectomy.
Egecioglu
Emil
E
Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, P.O. Box 434, SE-405 30 Göteborg, Sweden.
Stenström
Björn
B
Pinnock
Scarlett B
SB
Tung
Loraine Y C
LY
Dornonville de la Cour
Charlotta
C
Lindqvist
Andreas
A
Håkanson
Rolf
R
Syversen
Unni
U
Chen
Duan
D
Dickson
Suzanne L
SL
D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D005743:Gastrectomy; D005786:Gene Expression Regulation; D054439:Ghrelin / Q000494:pharmacology*; D007031:Hypothalamus / Q000378:metabolism*; D051379:Mice; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D013270:Stomach / Q000601:surgery*
D054369:Agouti-Related Protein; D054439:Ghrelin; D009478:Neuropeptide Y; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin