期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：10
页码：5628-5633
DOI：10.1073/pnas.1031698100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Intraperitoneal (i.p.) injection of C75, a fatty acid synthase inhibitor, causes a rapid ([≤]2-h) and persistent (to at least 24-h) {approx}95% decrease in food intake. The persistent effect seems to be due to inhibition of the fasting-induced up-regulation of expression of hypothalamic orexigenic neuropeptides neuropeptide Y and agouti-related protein and down-regulation of expression of anorexigenic neuropeptides pro-opiomelanocortin/-melanocyte-stimulating hormone and cocaine-amphetamine-related transcript. The effect of C75 on neuronal activity in the hypothalamus and brainstem was assessed by c-Fos expression. Consistent with its effect on neuropeptide expression, C75 blocked fasting-induced c-Fos expression in the arcuate nucleus (Arc), lateral hypothalamic area (LHA), and paraventricular nucleus (PVN) 10-24 h after i.p. injection. However, i.p. C75 induced a rapid ([≤]2-h) c-Fos expression in the nucleus of the solitary tract (NTS) and area postrema of the brainstem but not in the Arc or LHA. Intracerebroventricular administration of C75 rapidly induced c-Fos expression in the Arc, PVN, and NTS, supporting a central role of C75 in the regulation of food intake. Thus, suppression of food intake by C75 administered i.p. seems to be mediated in two phases, a rapid initial phase via the NTS/area postrema of the brainstem and a delayed phase via the Arc, LHA, and PVN of the hypothalamus. The delayed effect of C75 on the Arc, LHA, and PVN correlates well with its ability to interfere with the fasting-induced effects on the expression of key orexigenic (neuropeptide Y and agouti-related protein) and anorexigenic (pro-opiomelanocortin/-melanocyte-stimulating hormone and cocaine-amphetamine-related transcript) messages in the hypothalamus.
关键词：c- fos ‖arcuate nucleus‖paraventricular nucleus‖lateral hypothalamic area‖nucleus of the solitary tract/area postrema
