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Targeted Disruption of the Melanin-Concentrating Hormone Receptor-1 Results in Hyperphagia and Resistance to Diet-Induced Obesity
Open accessAbstract
The hypothalamic neuropeptide melanin-concentrating hormone (MCH) has been implicated in a variety of physiological functions including the regulation of feeding and energy homeostasis. Two MCH receptors (MCHR1 and MCHR2) have been identified so far. To decipher the functional role of the MCH receptors, we have generated and phenotypically characterized mice rendered deficient in MCHR1 expression by homologous recombination. Inactivation of MCHR1 results in mice (MCHR1-/-) that are resistant to diet-induced obesity. With a high-fat diet, body fat mass is significantly lower in both male (4.7 +/- 0.6 g vs. 9.6 +/- 1.2 g) and female (3.9 +/- 0.2 vs. 5.8 +/- 0.5 g) MCHR1-/- mice than that of the wild-type control (P < 0.01), but the lean mass remains constant. When normalized to body weight, female mice are hyperphagic, and male mice are hyperphagic and hypermetabolic, compared with wild-type mice. Consistent with the lower fat mass, both leptin and insulin levels are significantly lower in male MCHR1-/- mice than in the wild-type controls. Our data firmly establish MCHR1 as a mediator of MCH effects on energy homeostasis and suggest that inactivation of MCHR1 alone is capable to counterbalance obesity induced by a high-fat diet.
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Cites
Role of Nonexercise Activity Thermogenesis in Resistance to Fat Gain in Humans
Levine, J. A., Eberhardt, N. L., & Jensen, M. D. (1999) · Science · doi:10.1126/science.283.5399.212 · Cited by 997
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The neurobiology and control of anxious states
Millan, M. J. (2003) · Progress in Neurobiology · doi:10.1016/s0301-0082(03)00087-x · Cited by 965
Berbari, N. F., Lewis, J. S., Bishop, G. A., Askwith, C. C., & Mykytyn, K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711027105 · Cited by 474
Mukhopadhyay, S., Wen, X., Chih, B., Nelson, C. D., Lane, W. S., Scales, S. J., & Jackson, P. K. (2010) · Genes & Development · doi:10.1101/gad.1966210 · Cited by 435
Georgescu, D., Sears, R. M., Hommel, J. D., Barrot, M., Bolaños, C. A., Marsh, D. J., Bednarek, M. A., Bibb, J. A., Maratos-Flier, E., Nestler, E. J., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1714-04.2005 · Cited by 346
Mutant G-protein-coupled receptors as a cause of human diseases
Schöneberg, T., Schulz, A., Biebermann, H., Hermsdorf, T., Römpler, H., & Sangkuhl, K. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.08.008 · Cited by 337
Metadata
- Authors
- Chen, Y., Hu, C., Hsu, C.-K., Zhang, Q., Chen, B., Asnicar, M., Hsiung, H. M., Fox, N. W., Slieker, L. J., Yang, D. D., Heiman, M. L., & Shi, Y.
- Venue
- Endocrinology
- Publisher
- Oxford University Press
- Published
- 2002-07-01
- Volume
- 143
- Issue
- 7
- Pages
- 2469-2477
- ISSN
- 0013-7227 (ISSN-L)
- OpenAlex
- W2145718676
- Cited by
- 333
- References
- 1
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Chen, Y., Hu, C., Hsu, C.-K., Zhang, Q., Chen, B., Asnicar, M., Hsiung, H. M., Fox, N. W., Slieker, L. J., Yang, D. D., Heiman, M. L., & Shi, Y. (2002). Targeted Disruption of the Melanin-Concentrating Hormone Receptor-1 Results in Hyperphagia and Resistance to Diet-Induced Obesity. Endocrinology. https://doi.org/10.1210/en.143.7.2469
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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