Nature Medicine10, 524 - 529 (2004)
Published online: 11 April 2004; | doi:10.1038/nm1029
There is an Erratum (June 2004) associated with this Article.
Adiponectin acts in the brain to decrease body weight
Yong Qi1, Nobuhiko Takahashi1, Stanley M Hileman2, Hiralben R Patel1, Anders H Berg3, Utpal B Pajvani3, Philipp E Scherer3
& Rexford S Ahima1
1
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, and the Penn Diabetes Center, University of Pennsylvania, Philadelphia, Pennsylvania
19104, USA.
2
Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia
26506, USA.
3
Department of Cell Biology and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York
10461, USA.
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. Lepob/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 (Ay/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.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
