Egecioglu Emil, Stenström Björn, Pinnock Scarlett B, Tung Loraine Y C, Dornonville de la Cour Charlotta, Lindqvist Andreas, Håkanson Rolf, Syversen Unni, Chen Duan, Dickson Suzanne L
Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, P.O. Box 434, SE-405 30 Göteborg, Sweden.
Regul Pept. 2008 Feb 7;146(1-3):176-82. doi: 10.1016/j.regpep.2007.09.006. Epub 2007 Sep 14.
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.
我们研究了胃饥饿素缺乏(通过胃切除术)和/或用胃激素胃饥饿素进行治疗/替代,是否会以与胃饥饿素的促肥胖作用一致的方式,改变参与能量平衡的关键下丘脑基因的表达。术后2周,给小鼠注射胃饥饿素(12 nmol/小鼠/天,皮下注射)或赋形剂,持续8周。胃切除术对这些基因的表达影响不大,除了弓状核中神经肽Y(NPY)mRNA表达增加。给胃切除小鼠和假手术小鼠注射胃饥饿素,增加了促食欲肽NPY和刺鼠肽基因相关蛋白(AgRP)的mRNA表达,同时降低了厌食肽阿黑皮素原(POMC)的mRNA表达。用胃饥饿素模拟物MK-0677对大鼠进行两周灌胃治疗,增加了弓状核中NPY和POMC的mRNA以及下丘脑外侧区黑色素聚集激素(MCH)的mRNA表达。因此,虽然胃饥饿素和胃饥饿素模拟物激活了预测的促肥胖胃饥饿素信号通路,但这些通路在很大程度上不受胃切除术的影响。