The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity
Open accessAbstract
Beige adipocytes in white adipose tissue (WAT) are similar to classical brown adipocytes in that they can burn lipids to produce heat. Thus, an increase in beige adipocyte content in WAT browning would raise energy expenditure and reduce adiposity. Here we report that adipose-specific inactivation of Notch1 or its signaling mediator Rbpj in mice results in browning of WAT and elevated expression of uncoupling protein 1 (Ucp1), a key regulator of thermogenesis. Consequently, as compared to wild-type mice, Notch mutants exhibit elevated energy expenditure, better glucose tolerance and improved insulin sensitivity and are more resistant to high fat diet–induced obesity. By contrast, adipose-specific activation of Notch1 leads to the opposite phenotypes. At the molecular level, constitutive activation of Notch signaling inhibits, whereas Notch inhibition induces, Ppargc1a and Prdm16 transcription in white adipocytes. Notably, pharmacological inhibition of Notch signaling in obese mice ameliorates obesity, reduces blood glucose and increases Ucp1 expression in white fat. Therefore, Notch signaling may be therapeutically targeted to treat obesity and type 2 diabetes.
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Cites
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Identification and Importance of Brown Adipose Tissue in Adult Humans
Cypess, A. M., Lehman, S., Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y.-H., Doria, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810780 · Cited by 4,399
Cold-Activated Brown Adipose Tissue in Healthy Men
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Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human
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Functional Brown Adipose Tissue in Healthy Adults
Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., Taittonen, M., Laine, J., Savisto, N.-J., Enerbäck, S., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808949 · Cited by 3,058
Notch signalling: a simple pathway becomes complex
Bray, S. J. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2009 · Cited by 2,620
Adipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170
High Incidence of Metabolically Active Brown Adipose Tissue in Healthy Adult Humans
Saito, M., Okamatsu-Ogura, Y., Matsushita, M., Watanabe, K., Yoneshiro, T., Nio-Kobayashi, J., Iwanaga, T., Miyagawa, M., Kameya, T., Nakada, K., et al. (2009) · Diabetes · doi:10.2337/db09-0530 · Cited by 1,848
Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain
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FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis
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Cited by
Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis
Sidossis, L., & Kajimura, S. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78362 · Cited by 687
Beige adipocyte maintenance is regulated by autophagy-induced mitochondrial clearance
Altshuler-Keylin, S., Shinoda, K., Hasegawa, Y., Ikeda, K., Hong, H., Kang, Q., Yang, Y., Perera, R. M., Debnath, J., & Kajimura, S. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.002 · Cited by 349
Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis
Zhu, C., Kim, K., Wang, X., Bartolome, A., Salomao, M., Dongiovanni, P., Meroni, M., Graham, M. J., Yates, K. P., Diehl, A. M., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat0344 · Cited by 250
Xu, Y., Yu, T., Ma, G., Zheng, L., Jiang, X., Yang, F., Wang, Z., Li, N., He, Z., Song, X., et al. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.62556 · Cited by 110
Okla, M., Zaher, W., Alfayez, M., & Chung, S. (2018) · Inflammation · doi:10.1007/s10753-017-0718-y · Cited by 96
Metadata
- Authors
- Bi, P., Shan, T., Liu, W., Yue, F., Yang, X., Liang, X.-R., Wang, J., Li, J., Carlesso, N., Liu, X., & Kuang, S.
- Venue
- Nature Medicine
- Published
- 2014-07-20
- Volume
- 20
- Issue
- 8
- Pages
- 911-918
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1967661330
- Cited by
- 267
- References
- 69
- FWCI
- 16.13
- Type
- journal article
- Language
- en
- Open access
- green
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