Brown M, Bing C, King P, Pickavance L, Heal D, Wilding J
Department of Medicine, University of Liverpool, PO Box 147, Liverpool, L69 3GA.
Br J Pharmacol. 2001 Apr;132(8):1898-904. doi: 10.1038/sj.bjp.0704030.
We studied the effects of the novel noradrenaline and serotonin (5-HT) reuptake inhibitor sibutramine on feeding and body weight in a rat model of dietary obesity, and whether it interacts with hypothalamic neuropeptide Y (NPY) neurones. Chow-fed and dietary-obese (DIO) male Wistar rats were given sibutramine (3 mg kg(-1) day(-1) p.o.) or deionized water for 21 days. Sibutramine decreased food intake throughout the treatment period in both dietary-obese rats (P<0.0001) and lean rats (P<0.0001). Weight gain was reduced so that final body weight was 10% lower in dietary-obese (P<0.005) and 8% lower in lean (P<0.05) rats versus their untreated controls. Plasma leptin concentration was lower in sibutramine-treated dietary-obese rats (P<0.05), and in treated lean rats (P<0.05). Using the homeostasis model assessment (HOMA) as a measure of insulin resistance, untreated DIO rats were significantly more insulin resistant than controls (P<0.005), and this was corrected by sibutramine treatment (P<0.05). Neither hypothalamic NPY mRNA nor NPY peptide levels in a number of hypothalamic nuclei were significantly altered by sibutramine compared to untreated controls. The hypophagic and anti-obesity effects of sibutramine in dietary-obese Wistar rats appear not to be mediated by inhibition of ARC NPY neurones.
我们研究了新型去甲肾上腺素和5-羟色胺（5-HT）再摄取抑制剂西布曲明对饮食性肥胖大鼠模型进食和体重的影响，以及它是否与下丘脑神经肽Y（NPY）神经元相互作用。给正常进食和饮食性肥胖（DIO）的雄性Wistar大鼠灌胃西布曲明（3 mg kg⁻¹ 每日 口服）或去离子水，持续21天。在整个治疗期间，西布曲明均降低了饮食性肥胖大鼠（P<0.0001）和瘦大鼠（P<0.0001）的食物摄入量。体重增加减少，与未治疗的对照组相比，饮食性肥胖大鼠的最终体重降低了10%（P<0.005），瘦大鼠降低了8%（P<0.05）。西布曲明治疗的饮食性肥胖大鼠（P<0.05）和治疗的瘦大鼠（P<0.05）的血浆瘦素浓度较低。使用稳态模型评估（HOMA）作为胰岛素抵抗的指标，未治疗的DIO大鼠比对照组的胰岛素抵抗明显更强（P<0.005），而西布曲明治疗可纠正这一情况（P<0.05）。与未治疗的对照组相比，西布曲明对多个下丘脑核团的下丘脑NPY mRNA和NPY肽水平均无显著影响。西布曲明对饮食性肥胖Wistar大鼠的食欲减退和抗肥胖作用似乎不是通过抑制弓状核NPY神经元介导的。
