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Adiponectin acts in the brain to decrease body weight

Nature Medicine volume 10, pages 524–529 (2004)Cite this article

An Erratum to this article was published on 01 June 2004

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.

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Figure 1: Effects of i.c.v. ADP on C57Bl/6J mice.
Figure 2: Comparison of hypothalamic responses to central and systemic ADP and leptin.
Figure 3: Effects of ADP or leptin (3 μg/g), or ADP together with leptin, administered i.c.v. into Lepob/ob mice.
Figure 4: Lack of effect of i.c.v. ADP and leptin (0.1 μg/g) on Ay/a mice.

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Acknowledgements

These studies were supported by National Institutes of Health grants RO1-DK62348 (to R.S.A.) and R01-DK55758 (to P.E.S.), Medical Scientist Training Grant T32-GM07288 (to U.B.P.) and an American Diabetes Medical Scientist Training Grant (to A.H.B.). Technical expertise for mouse studies was provided by the Penn Diabetes Center Mouse Phenotyping Core (funded by National Institutes of Health grant P30-DK19525). We thank N. Llanza for RT-PCR analysis.

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Authors and Affiliations

  1. Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, and the Penn Diabetes Center, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Yong Qi, Nobuhiko Takahashi, Hiralben R Patel & Rexford S Ahima

  2. Department of Physiology and Pharmacology, West Virginia University, Morgantown, 26506, West Virginia, USA

    Stanley M Hileman

  3. Department of Cell Biology and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, 10461, New York, USA

    Anders H Berg, Utpal B Pajvani & Philipp E Scherer

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  1. Yong Qi
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Correspondence to Rexford S Ahima.

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Qi, Y., Takahashi, N., Hileman, S. et al. Adiponectin acts in the brain to decrease body weight. Nat Med 10, 524–529 (2004). https://doi.org/10.1038/nm1029

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