Adiponectin acts in the brain to decrease body weight

被引:664
作者
Qi, Y
Takahashi, N
Hileman, SM
Patel, HR
Berg, AH
Pajvani, UB
Scherer, PE
Ahima, RS [1 ]
机构
[1] Univ Penn, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA
[2] Univ Penn, Penn Diabet Ctr, Philadelphia, PA 19104 USA
[3] W Virginia Univ, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA
[4] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA
[5] Albert Einstein Coll Med, Ctr Diabet Res & Training, Bronx, NY 10461 USA
关键词
D O I
10.1038/nm1029
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Adiponectin (ADP) is an adipocyte hormone involved in glucose and lipid metabolism. We detected a rise in ADP in cerebrospinal fluid after intravenous (i.v.) injection, consistent with brain transport. In contrast to leptin, intracerebroventricular (i.c.v.) administration of ADP decreased body weight mainly by stimulating energy expenditure. Full-length ADP, mutant ADP with Cys39 replaced with serine, and globular ADP were effective, whereas the collagenous tail fragment was not. Lep(ob/ob) mice were especially sensitive to i.c.v. and systemic ADP, which resulted in increased thermogenesis, weight loss and reduction in serum glucose and lipid levels. ADP also potentiated the effect of leptin on thermogenesis and lipid levels. While both hormones increased expression of hypothalamic corticotropin-releasing hormone (CRH), ADP had no substantial effect on other neuropeptide targets of leptin. In addition, ADP induced distinct Fos immunoreactivity. Agouti (A(y)/a) mice did not respond to ADP or leptin, indicating the melanocortin pathway may be a common target. These results show that ADP has unique central effects on energy homeostasis.
引用
收藏
页码:524 / 529
页数:6
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