Morris M J, Tortelli C F, Filippis A, Proietto J
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Regul Pept. 1998 Sep 25;75-76:441-7. doi: 10.1016/s0167-0115(98)00100-1.
Neuropeptide Y (NPY) exerts effects on food intake at the level of the paraventricular nucleus (PVN), which receives a dense projection from the arcuate nucleus. Monosodium glutamate (MSG) has been shown to induce hyperadiposity despite hypophagia associated with chemical ablation of the arcuate nucleus. We investigated the mechanism for the excess fat accumulation by studying the time course of changes in brain NPY content, food intake, leptin levels and BAT GLUT4 content after neonatal MSG treatment. Male rat pups were injected with MSG or saline vehicle on days 2, 4, and 6 and examined at 30 and 90 days. Plasma leptin, body mass, length, adipose tissue mass and brown fat GLUT4 were measured and brains dissected for measurement of NPY content. By 30 days, NPY concentrations were reduced in the arcuate nucleus and anterior hypothalamus, and animals tended to be hypophagic. Peripheral adipose tissue levels were less than controls, in line with their low leptin concentrations. At 90 days, MSG treatment was associated with marked reductions in NPY concentrations in several hypothalamic areas, including the PVN and arcuate nucleus, along with increased adiposity and plasma leptin. Animals also displayed marked hypophagia. Levels of GLUT4 transporter were reduced in brown adipose tissue at both ages. The early decrease in brown fat GLUT4 suggests an impairment of the hypothalamic sympathetic input to brown fat which disrupts thermogenesis, contributing to the development of adiposity in the presence of hypophagia.
神经肽Y（NPY）在室旁核（PVN）水平上对食物摄入产生影响，室旁核接受来自弓状核的密集投射。尽管谷氨酸单钠（MSG）与弓状核化学消融相关的食欲减退，但已显示其会诱导肥胖。我们通过研究新生期MSG处理后大脑NPY含量、食物摄入、瘦素水平和棕色脂肪GLUT4含量的变化时间进程，来探究脂肪过度积累的机制。雄性幼鼠在第2、4和6天注射MSG或生理盐水载体，并在30天和90天时进行检查。测量血浆瘦素、体重、体长、脂肪组织质量和棕色脂肪GLUT4，并解剖大脑以测量NPY含量。到30天时，弓状核和下丘脑前部的NPY浓度降低，动物倾向于食欲减退。外周脂肪组织水平低于对照组，与其低瘦素浓度一致。在90天时，MSG处理与包括室旁核和弓状核在内的几个下丘脑区域的NPY浓度显著降低有关，同时肥胖和血浆瘦素增加。动物也表现出明显的食欲减退。两个年龄段的棕色脂肪组织中GLUT4转运蛋白水平均降低。棕色脂肪GLUT4的早期降低表明下丘脑对棕色脂肪的交感神经输入受损，这会破坏产热，导致在食欲减退的情况下肥胖的发展。
