Cerulenin mimics effects of leptin on metabolic rate, food intake, and body weight independent of the melanocortin system, but unlike leptin, cerulenin fails to block neuroendocrine effects of fasting

被引:65
作者
Makimura, H
Mizuno, TM
Yang, XJ
Silverstein, J
Beasley, J
Mobbs, CV
机构
[1] CUNY Mt Sinai Sch Med, Neurobiol Aging Labs, Fishberg Ctr Neurobiol, Dept Geriatr, New York, NY 10029 USA
[2] CUNY Mt Sinai Sch Med, Neurobiol Aging Labs, Fishberg Ctr Neurobiol, Dept Anesthesia, New York, NY 10029 USA
关键词
D O I
10.2337/diabetes.50.4.733
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cerulenin and a related compound, C75, have recently been reported to reduce food intake and body weight independent of leptin through a mechanism hypothesized, like leptin, to involve hypothalamic nutrition-sensitive neurons. To assess whether these inhibitors act through mechanisms similar to mechanisms engaged by leptin, ob/ob and A(y) (agouti) mice, as well as fed and fasted wild-type mice, were treated with cerulenin. Like leptin, cerulenin reduced body weight and food intake and increased metabolic rate in ob/ob mice, and cerulenin produced the same effects in wild-type mice, whereas lithium chloride, at doses that produce conditioned taste aversion, reduced metabolic rate. However, in contrast to leptin, cerulenin did not prevent effects of fasting on plasma corticosterone or hypothalamic levels of neuropeptide Y, agouti-related peptide, pro-opiomefanocortin, or cocaine- and amphetamine-related peptide mRNA. Also, in contrast to leptin, cerulenin was highly effective to reduce body weight in A(y) mice, in which obesity is caused by blockade of the melanocortin receptor. These data demonstrate that cerulenin produces metabolic effects similar to effects of leptin, but through mechanisms that are independent of, or down-stream from, both leptin and melanocortin receptors.
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收藏
页码:733 / 739
页数:7
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