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Cited by 548

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Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism

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Marsh, Donald J., Weingarth, Drew T., Novi, Dawn E., Chen, Howard Y., Trumbauer, Myrna E., Chen, Airu S., Guan, Xiao-Ming, Jiang, Michael M., Feng, Yue, Camacho, Ramon E., Shen, Zhu, Frazier, Easter G., Yu, Hong, Metzger, Joseph M., Kuca, Stephanie J., Shearman, Lauren P., Gopal-Truter, Shobhna, MacNeil, Douglas J., Strack, Alison M., MacIntyre, D. Euan, Van der Ploeg, Lex H. T., Qian, Su·2002·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.052706899
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Abstract

Melanin-concentrating hormone (MCH) is a cyclic 19-aa hypothalamic neuropeptide derived from a larger prohormone precursor of MCH (Pmch), which also encodes neuropeptide EI (NEI) and neuropeptide GE (NGE). Pmch-deficient ( Pmch −/− ) mice are lean, hypophagic, and have an increased metabolic rate. Transgenic mice overexpressing Pmch are hyperphagic and develop mild obesity. Consequently, MCH has been implicated in the regulation of energy homeostasis. The MCH 1 receptor (MCH1R) is one of two recently identified G protein-coupled receptors believed to be responsible for the actions of MCH. We evaluated the physiological role of MCH1R by generating MCH1R-deficient ( Mch1r −/− ) mice. Mch1r −/− mice have normal body weights, yet are lean and have reduced fat mass. Surprisingly, Mch1r −/− mice are hyperphagic when maintained on regular chow, and their leanness is a consequence of hyperactivity and altered metabolism. Consistent with the hyperactivity, Mch1r −/− mice are less susceptible to diet-induced obesity. Importantly, chronic central infusions of MCH induce hyperphagia and mild obesity in wild-type mice, but not in Mch1r −/− mice. We conclude that MCH1R is a physiologically relevant MCH receptor in mice that plays a role in energy homeostasis through multiple actions on locomotor activity, metabolism, appetite, and neuroendocrine function.

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Authors
Marsh, D. J., Weingarth, D. T., Novi, D. E., Chen, H. Y., Trumbauer, M. E., Chen, A. S., Guan, X.-M., Jiang, M. M., Feng, Y., Camacho, R. E., Shen, Z., Frazier, E. G., Yu, H., Metzger, J. M., Kuca, S. J., Shearman, L. P., Gopal-Truter, S., MacNeil, D. J., Strack, A. M., MacIntyre, D. E., Van der Ploeg, L. H. T., & Qian, S.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2002-02-26
Volume
99
Issue
5
Pages
3240-3245
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.052706899
OpenAlex
W2166745166
Cited by
548
References
0
FWCI
12.08
Type
journal article
Language
en
Open access
green

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