The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis
Open accessAbstract
Uncoupling protein 1 (UCP1) plays a central role in nonshivering thermogenesis in brown fat; however, its role in beige fat remains unclear. Here we report a robust UCP1-independent thermogenic mechanism in beige fat that involves enhanced ATP-dependent Ca2+ cycling by sarco/endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) and ryanodine receptor 2 (RyR2). Inhibition of SERCA2b impairs UCP1-independent beige fat thermogenesis in humans and mice as well as in pigs, a species that lacks a functional UCP1 protein. Conversely, enhanced Ca2+ cycling by activation of α1- and/or β3-adrenergic receptors or the SERCA2b–RyR2 pathway stimulates UCP1-independent thermogenesis in beige adipocytes. In the absence of UCP1, beige fat dynamically expends glucose through enhanced glycolysis, tricarboxylic acid metabolism and pyruvate dehydrogenase activity for ATP-dependent thermogenesis through the SERCA2b pathway; beige fat thereby functions as a 'glucose sink' and improves glucose tolerance independently of body weight loss. Our study uncovers a noncanonical thermogenic mechanism through which beige fat controls whole-body energy homeostasis via Ca2+ cycling.
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Cites
High Incidence of Metabolically Active Brown Adipose Tissue in Healthy Adult Humans
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Self-citationMice lacking mitochondrial uncoupling protein are cold-sensitive but not obese
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Self-citationMechanism of Fatty-Acid-Dependent UCP1 Uncoupling in Brown Fat Mitochondria
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Cited by
The Common and Distinct Features of Brown and Beige Adipocytes
Ikeda, K., Maretich, P., & Kajimura, S. (2018) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2018.01.001 · Cited by 543
Self-citationLipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics
Morigny, P., Boucher, J., Arner, P., & Langin, D. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00471-8 · Cited by 527
Energy metabolism in health and diseases
Liu, H., Wang, S., Wang, J., Guo, X., Song, Y., Fu, K., Gao, Z., Liu, D., He, W., & Yang, L.-L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02141-x · Cited by 399
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CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling
Oguri, Y., Shinoda, K., Kim, H., Alba, D. L., Bolus, W. R., Wang, Q., Brown, Z., Pradhan, R. N., Tajima, K., Yoneshiro, T., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.021 · Cited by 284
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Metadata
- Authors
- Ikeda, K., Kang, Q., Yoneshiro, T., Camporez, J. P., Maki, H., Homma, M., Shinoda, K., Chen, Y., Lu, X., Maretich, P., Tajima, K., Ajuwon, K. M., Soga, T., & Kajimura, S.
- Venue
- Nature Medicine
- Published
- 2017-11-13
- Volume
- 23
- Issue
- 12
- Pages
- 1454-1465
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2768810688
- Cited by
- 652
- References
- 9
- FWCI
- 34.85
- Type
- journal article
- Language
- en
- Open access
- green
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- Ikeda, K., Kang, Q., Yoneshiro, T., Camporez, J. P., Maki, H., Homma, M., Shinoda, K., Chen, Y., Lu, X., Maretich, P., Tajima, K., Ajuwon, K. M., Soga, T., & Kajimura, S. (2017). UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis. Nature Medicine. https://doi.org/10.1038/nm.4429
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