Nature 380, 243 - 247 (21 March 1996); doi:10.1038/380243a0

A role for melanin-concentrating hormone in the central regulation of feeding behaviour

Daqing Qu, David S. Ludwig^*, Steen Gammeltoft^†, Megan Piper, Mary Ann Pelleymounter^‡, Mary Jane Cullen^‡, Wendy Foulds Mathes^§, Jeanne Przypek^§, Robin Kanarek^§ & Eleftheria Maratos-Flier

Research Laboratory, Joslin Diabetes Center, and Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA
^*Department of Medicine, Division of Endocrinology, Beth Israel Hospital, Boston, Massachusetts 02215, USA
^‡Department of Neurobiology, Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California 91320, USA
^§Department of Psychology, Tufts University, Medford, Massachusetts 2155,USA
To whom correspondence should be addressed.
^†Present address: Department of Clinical Chemistry, Glostrup Hospital, University of Copenhagen Medical chool, Dk2600 Glostrup, Denmark.

THE hypothalamus plays a central role in the integrated regulation of energy homeostasis and body weight, and a number of hypothalamic neuropeptides, such as neuropeptide Y (ref. 1), galanin², CRH (ref. 3), and GLP-1 (ref. 4), have been implicated in the mediation of these effects. To discover new hypothalamic peptides involved in the regulation of body weight, we used differential display polymerase chain reaction⁵ to identify messenger RNAs that are differentially expressed in the hypothalamus of ob/+ compared with ob/ob C57B1/6J mice. We show here that one mRNA that is overexpressed in the hypothalamus of ob/ob mice encodes the neuropeptide melanin-concentrating hormone (MCH). Fasting further increased expression of MCH mRNA in both normal and obese animals. Neurons containing MCH are located in the zona incerta and in the lateral hypothalamus. These areas are involved in regulation of ingestive behaviour, but the role of MCH in mammalian physiology is unknown. To determine whether MCH is involved in the regulation of feeding, we injected MCH into the lateral ventricles of rats and found that their food consumption increased. These findings suggest that MCH participates in the hypothalamic regulation of body weight.

References

1.	Stanley, B. G., Anderson, K. C., Grayson, M. H. & Leibowitz, S. F. Physiol. Behav. 46, 173−177 (1989). | Article | PubMed | ChemPort |
2.	Kyrkouli, S. E., Stanley, B. G. & Leibowitz, S. F. Eur. J. Pharmacol. 122, 159−160 (1986). | Article | PubMed | ChemPort |
3.	Arase, K., York, D. A., Shimizu, H., Shargill, N. & Bray, G. A. Am. J. Physiol. 255, E255−259 (1988). | PubMed | ISI | ChemPort |
4.	Turton, M. D. et al. Nature 379, 69−72 (1996). | Article | PubMed | ISI | ChemPort |
5.	Liang, P. & Pardee, A. B. Science 257, 967−971 (1992). | PubMed | ISI | ChemPort |
6.	Nahon, J. L., Presse, F., Breton, C., Herview, G. & Schorpp, M. Ann. N.Y. Acad. Sci. 680, 111−129 (1993). | PubMed | ChemPort |
7.	Breton, C., Presse, F., Hervieu, G. & Nahon, J. L. Molec. cell. Neurosci. 4, 271−284 (1993). | ChemPort |
8.	Tempel, D. L. & Leibowitz, S. F. Brain Res. Bull. 25, 821−825 (1990). | Article | PubMed | ChemPort |
9.	Kawauchi, H., Kawazoe, M., Tsubplawa, M., Kishida, M. & Baker, B. I. Nature 305, 423−432 (1983).
10.	Kawauchi, H., Naito, N. & Ono, M. Ann. N.Y. Acad. Sci. 680, 64−77 (1993). | PubMed | ChemPort |
11.	Skofitsch, G., Jacobowitz, D. M. & Zamir, N. Brain Res. Bull. 15, 635−639 (1985). | Article | PubMed | ISI | ChemPort |
12.	Zamir, N., Skofitsch, G., Bannon, M. J. & Jacobowitz, D. M. Proc. natn. Acad. Sci. U.S.A. 83, 1528−1531 (1986). | ChemPort |
13.	Naito, N., Kawazoe, I., Nakai, Y. & Kawauchi, H. Cell Tissue Res. 253, 291−295 (1988). | PubMed | ChemPort |
14.	Thompson, R. C. & Watson, S. J. DNA Cell Biol. 9, 637−645 (1990). | PubMed | ChemPort |
15.	Bittencourt, J. C. et al. J. comp. Neurol. 319, 218−245 (1992). | Article | PubMed | ISI | ChemPort |
16.	Nahon, J. L., Presse, F., Bittencourt, J. C., Sawchenko, P. E. & Vale, W. Endocrinology 125, 2056−2065 (1989). | PubMed | ISI | ChemPort |
17.	Parkes, D. G. & Vale, W. Endocrinology 131, 1826−1831 (1992). | Article | PubMed | ChemPort |
18.	Risold, P. Y., Fellmann, D., Rivier, J., Vale, W. & Bugnon, C. Neurosci. Lett. 136, 145−149 (1992). | Article | PubMed | ChemPort |
19.	Oomura, Y. New Physiol. Sci. 2, 199−203 (1987). | ChemPort |
20.	Cechetto, D. F. & Saper, C. B. J. comp. Neurol. 272, 579−604 (1988). | Article | PubMed | ChemPort |
21.	Rance, T. & Baker, B. I. Gen. comp. Endocrin. 37, 64−73 (1979). | Article | ChemPort |
22.	Matsunaga, T. O., Hruby, V. I., Lebl, M., De Lauro Castrucci, A. M. & Hadley, M. E. Peptides 10, 773−778 (1989). | Article | PubMed | ChemPort |
23.	Cone, R. D. et al. Ann. N.Y. Acad. Sci. 80, 342−363 (1993).
24.	Bultman, S. J., Michaud, E. J. & Woychik, R. P. Cell 75, 1195−1204 (1992).
25.	Klebrig, M. L., Wilkinson, J. E., Geisler, J. G. & Woychik, R. P. Proc. natn. Acad. Sci. U.S.A. 92, 4728−4732 (1995).
26.	Lu, D. et al. Nature 371, 799−803 (1994). | Article | PubMed | ISI | ChemPort |
27.	Zhang, Y. et al. Nature 372, 425−432 (1994). | Article | PubMed | ISI | ChemPort |
28.	Pelleymounter, M. A. et al. Science 269, 540−543 (1995). | PubMed | ISI | ChemPort |
29.	Jakubowski, M. & Roberts, R. L. J. Neuroendocrin. Appendix 2 (1991).
30.	Sanacora, G., Kershaw, M., Finkelstein, J. A. & White, J. D. Endocrinology 127, 730−736 (1990). | PubMed | ISI | ChemPort |