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Hypothalamic CART is a new anorectic peptide regulated by leptin

Nature volume 393, pages 72–76 (1998)Cite this article

Abstract

The mammalian hypothalamus strongly influences ingestive behaviour through several different signalling molecules and receptor systems1,2,3,4. Here we show that CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide5,6,7,8, is a satiety factor and is closely associated with the actions of two important regulators of food intake, leptin and neuropeptide Y. Food-deprived animals show a pronounced decrease in expression of CART messenger RNA in the arcuate nucleus. In animal models of obesity with disrupted leptin signalling, CART mRNA is almost absent from the arcuate nucleus. Peripheral administration of leptin to obese mice stimulates CART mRNA expression. When injected intracerebroventricularly into rats, recombinant CART peptide inhibits both normal and starvation-induced feeding, and completely blocks the feeding response induced by neuropeptide Y. An antiserum against CART increases feeding in normal rats, indicating that CART may be an endogenous inhibitor of food intake in normal animals.

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Figure 1: Expression of CART mRNA in obese rats and mice.
Figure 2: CART mRNA expression is induced by leptin.
Figure 3: Quantification of CART mRNA in situ hybridization in sections from the hypothalamus of non-fasted (filled bars) and fasted (open bars) Wistar rats.
Figure 4: CART reduces food intake.
Figure 5: CART is present in neurons of the hypothalamic arcuate nucleus.

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Acknowledgements

We thank J. Kuijper for the gift of recombinant leptin; I. Diers, A. S. Andersen and P.F. Nielsen for production of CART in yeast and characterization of the purified peptide; and E. Bentsen, B. Jørgensen, W. Listov-Saabye, L.-L. Kruse, J. Mandelbaum, H. Petersen, L. Priskorn and S. Kryger for technical assistance. P.B.J. and O.D.M. were supported by the Danish Cancer Society and the Danish National Research Foundation. Hagedorn Research Institute is a basic research component of Novo Nordisk A/S. P.J.L. and N.V. were supported by the Danish Medical Research Council, the Danish Diabetes Association and the Novo Nordisk Foundation.

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Authors and Affiliations

  1. Health Care Discovery, Novo Nordisk A/S, Novo Alle, 6A1.47, DK-2880, Bagsvaerd, Denmark

    Peter Kristensen, Martin E. Judge, Lars Thim, Ulla Ribel, Kennet N. Christjansen, Birgitte S. Wulff, Jes T. Clausen & Sven Hastrup

  2. Hagedorn Research Institute, Niels Steensevej 6, DK-2820, Gentofte, Denmark

    Per B. Jensen & Ole D. Madsen

  3. Department of Anatomy, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N., Denmark

    Niels Vrang & Philip J. Larsen

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  1. Peter Kristensen
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Correspondence to Peter Kristensen.

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Kristensen, P., Judge, M., Thim, L. et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 393, 72–76 (1998). https://doi.org/10.1038/29993

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