The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
The Creb1 coactivator Crtc1 is required for energy balance and fertility
Open accessAbstract
The adipocyte-derived hormone leptin maintains energy balance by acting on hypothalamic leptin receptors (Leprs) that act on the signal transducer and activator of transcription 3 (Stat3). Although disruption of Lepr-Stat3 signaling promotes obesity in mice, other features of Lepr function, such as fertility, seem normal, pointing to the involvement of additional regulators. Here we show that the cyclic AMP responsive element–binding protein-1 (Creb1)-regulated transcription coactivator-1 (Crtc1) is required for energy balance and reproduction—Crtc1−/− mice are hyperphagic, obese and infertile. Hypothalamic Crtc1 was phosphorylated and inactive in leptin-deficient ob/ob mice, while leptin administration increased amounts of dephosphorylated nuclear Crtc1. Dephosphorylated Crtc1 stimulated expression of the Cartpt and Kiss1 genes, which encode hypothalamic neuropeptides that mediate leptin's effects on satiety and fertility. Crtc1 overexpression in hypothalamic cells increased Cartpt and Kiss1 gene expression, whereas Crtc1 depletion decreased it. Indeed, leptin enhanced Crtc1 activity over the Cartpt and Kiss1 promoters in cells overexpressing Lepr, and these effects were disrupted by expression of a dominant-negative Creb1 polypeptide. As leptin administration increased recruitment of hypothalamic Crtc1 to Cartpt and Kiss1 promoters, our results indicate that the Creb1-Crtc1 pathway mediates the central effects of hormones and nutrients on energy balance and fertility.
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Cites
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley, M. A., Smart, J. L., Rubinstein, M., Cerdán, M. G., Diano, S., Horvath, T. L., Cone, R. D., & Low, M. J. (2001) · Nature · doi:10.1038/35078085 · Cited by 2,356
Mechanisms of leptin action and leptin resistance.
Myers, M. G., Cowley, M. A., & Münzberg, H. (2008) · Annual Review of Physiology · doi:10.1146/annurev.physiol.70.113006.100707 · Cited by 1,074
Han, S.-K., Gottsch, M. L., Lee, K. J., Popa, S. M., Smith, J. T., Jakawich, S. K., Clifton, D. K., Steiner, R. A., & Herbison, A. E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3328-05.2005 · Cited by 1,036
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Self-citationGlucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity
Parton, L. E., Ye, C. P., Coppari, R., Enriori, P. J., Choi, B., Zhang, C.-Y., Xu, C., Vianna, C. R., Balthasar, N., Lee, C. E., et al. (2007) · Nature · doi:10.1038/nature06098 · Cited by 700
Cited by
CREB and the CRTC co-activators: sensors for hormonal and metabolic signals
Altarejos, J. Y., & Montminy, M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3072 · Cited by 1,040
Self-citationKisspeptins and Reproduction: Physiological Roles and Regulatory Mechanisms
Pinilla, L., Aguilar, E., Dieguez, C., Millar, R. P., & Tena-Sempere, M. (2012) · Physiological Reviews · doi:10.1152/physrev.00037.2010 · Cited by 801
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
The GIANT Consortium, Elks, C. E., Perry, J. R. B., Sulem, P., Chasman, D. I., Franceschini, N., He, C., Lunetta, K. L., Visser, J. A., Byrne, E. M., et al. (2010) · Nature Genetics · doi:10.1038/ng.714 · Cited by 504
Turcot, V., Lu, Y., Highland, H. M., Schurmann, C., Justice, A. E., Fine, R. S., Bradfield, J. P., Esko, T., Giri, A., Graff, M., et al. (2018) · Nature Genetics · doi:10.1038/s41588-017-0011-x · Cited by 409
Striatal microRNA controls cocaine intake through CREB signalling
Hollander, J. A., Im, H.-I., Amelio, A. L., Kocerha, J., Bali, P., Lu, Q., Willoughby, D., Wahlestedt, C., Conkright, M. D., & Kenny, P. J. (2010) · Nature · doi:10.1038/nature09202 · Cited by 388
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Metadata
- Authors
- Altarejos, J. Y., Goebel, N., Conkright, M. D., Inoue, H., Xie, J., Arias, C. M., Sawchenko, P. E., & Montminy, M.
- Venue
- Nature Medicine
- Published
- 2008-08-31
- Volume
- 14
- Issue
- 10
- Pages
- 1112-1117
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2051435398
- Cited by
- 199
- References
- 5
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- green
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