Churruca I, Portillo M P, Casis L, Gutiérrez A, Macarulla M T, Echevarría E
Department of Nutrition and Food Science, University of the Basque Country, Paseo de la Universidad 7, Vitoria, Spain.
Neuropeptides. 2008 Jun;42(3):293-9. doi: 10.1016/j.npep.2008.02.002. Epub 2008 Mar 21.
The aim of the present work was to study the potential involvement of melanocortin system in the anorectic mechanism of fluoxetine, a selective serotonin reuptake inhibitors, in obese Zucker rats. Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg; i.p.) daily for two weeks. The control group was given 0.9% NaCl solution. RT-PCR for pro-opiomelanocortin (POMC), Agouti gene related peptide (AgRP) and melanocortin receptor 4 (MC4-R) in the hypothalamus, as well as regional immunostaining for alpha-melanocyte stimulating hormone (alpha-MSH) and MC4-R were carried out. Fluoxetine administration increased POMC expression and reduced MC4-R expression in the hypothalamus, without changes in AgRP mRNA levels. Moreover, an increase in the numbers of alpha-MSH positively immunostained neural cells in the hypothalamic arcuate nucleus (ARC), as well as a significant decrease in the numbers of neural cells positively immunostained for MC4-R in the paraventricular nucleus (PVN), without changes in lateral hypothalamic area (LHA), were observed. These results suggest the involvement of alpha-MSH in central fluoxetine anorectic action.
本研究的目的是探讨黑素皮质素系统在选择性5-羟色胺再摄取抑制剂氟西汀对肥胖Zucker大鼠的厌食机制中的潜在作用。雄性肥胖Zucker（fa/fa）大鼠每天腹腔注射氟西汀（10mg/kg），持续两周。对照组给予0.9%氯化钠溶液。检测下丘脑促阿片黑素皮质素原（POMC）、刺鼠基因相关肽（AgRP）和黑素皮质素受体4（MC4-R）的RT-PCR，以及α-黑素细胞刺激素（α-MSH）和MC4-R的区域免疫染色。给予氟西汀可增加下丘脑POMC表达并降低MC4-R表达，而AgRP mRNA水平无变化。此外，观察到下丘脑弓状核（ARC）中α-MSH阳性免疫染色神经细胞数量增加，室旁核（PVN）中MC4-R阳性免疫染色神经细胞数量显著减少，而下丘脑外侧区（LHA）无变化。这些结果表明α-MSH参与了氟西汀的中枢厌食作用。
