Shimizu Hiroyuki, Oh-I Sinsuke, Okada Shuichi, Mori Masatomo
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
Endocr J. 2009;56(4):537-43. doi: 10.1507/endocrj.k09e-117. Epub 2009 May 20.
Nesfatin/nucleobindin 2 (NUCB2) is expressed in the appetite-control hypothalamic nuclei and brainstem nuclei. Nesfatin/NUCB2 expression in the paraventricular nucleus of the hypothalamus was modulated by starvation and refeeding. Intracerebroventricular administration of nesfatin-1 dose-dependently inhibited food intake for 6 hours in male Wistar and leptin resistant, Zucker fatty rats. Intraperitoneal administration of nesfatin-1 and its mid-segment (M30) dosedependentlyinhibited food intake for 3 hours in male ICR mice. Intraperitoneal administration of M30 also decreased foodintake in leptin-resistant, genetically obese (ob/ob), diabetic (db/db) mice and mice fed a 45% high fat diet for 28 days. Intraperitoneal administration of M30 increased proopiomelanocortin and cocaine- and amphetamine- related peptide mRNA expression in the nucleus of the solitary tract of mice. In addition, intranasal administration of nesfatin-1 significantly inhibited food intake for 6 hours in male Wistar rats. We summarize recent observations about nesfatin-1, and attempt to present future direction of nesfatin-1 research for developing a new anti-obesity treatment.
内脂素/核结合蛋白2(NUCB2)在下丘脑食欲控制核团和脑干核团中表达。饥饿和再喂养可调节下丘脑室旁核中内脂素/NUCB2的表达。在雄性Wistar大鼠和瘦素抵抗的Zucker肥胖大鼠中,脑室内注射内脂素-1可剂量依赖性地抑制6小时的食物摄取。在雄性ICR小鼠中,腹腔注射内脂素-1及其中段(M30)可剂量依赖性地抑制3小时的食物摄取。腹腔注射M30还可减少瘦素抵抗的遗传性肥胖(ob/ob)、糖尿病(db/db)小鼠以及喂食45%高脂饮食28天的小鼠的食物摄取。腹腔注射M30可增加小鼠孤束核中阿片促黑素皮质素原和可卡因及苯丙胺调节转录肽的mRNA表达。此外,在雄性Wistar大鼠中,鼻内给予内脂素-1可显著抑制6小时的食物摄取。我们总结了关于内脂素-1的最新观察结果,并试图提出内脂素-1研究未来开发新型抗肥胖治疗方法的方向。