Adiponectin acts in the brain to decrease body weight

Yong Qi, Nobuhiko Takahashi, Stanley M. Hileman, Hiralben R. Patel, Anders H. Berg, Utpal B. Pajvani, Philipp E. Scherer, Rexford S. Ahima

Research output: Contribution to journalArticle

611 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)524-529
Number of pages6
JournalNature medicine
Volume10
Issue number5
DOIs
StatePublished - May 2004

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Qi, Y., Takahashi, N., Hileman, S. M., Patel, H. R., Berg, A. H., Pajvani, U. B., Scherer, P. E., & Ahima, R. S. (2004). Adiponectin acts in the brain to decrease body weight. Nature medicine, 10(5), 524-529. https://doi.org/10.1038/nm1029