The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Functional thermogenic beige adipogenesis is inducible in human neck fat
Open accessAbstract
Background:Recent studies suggest human neck brown adipose tissue (BAT) to consist of ‘brown adipocyte (BA)-like’ or beige adipocytes. However, little is known about their thermogenic function. Within the beige adipocyte transcriptome, fibroblast growth factor-21 (FGF21) is a gene whose protein product acts as an adipokine, regulating cold-induced thermogenesis in animals. Here, we explored (i) the adipogenic potential, thermogenic function and FGF21 secretory capacity of beige adipocytes derived from human neck fat and (ii) the role of FGF21 in modulating adipose bioenergetics.Methods:Progenitors isolated from human cervical fat were differentiated into adipocytes with either a BA-like or white adipocyte (WA) phenotype. FGF21 secretion was measured by enzyme-linked immuosorbent assay. Real-time PCR/western blotting was used to determine cellular mRNA/protein levels. Extracellular flux bioanalyzer was used to quantify adipocyte oxygen consumption and fatty acid oxidation. Adipocyte heat production was measured by infrared thermography.Results:Under hormonal manipulation, primary human neck pre-adipocytes differentiated into adipocytes with either BA-like or WA phenotypes, on gene/protein and functional levels. BA-like cells expressed beige but not classic BA markers. During BA differentiation, FGF21 gene expression and secretion were increased, and were augmented following norepinephrine exposure (a cold mimic in vitro). Differentiated WA expressed β-klotho, a critical co-factor mediating FGF21 action. Treatment of WA with FGF21-induced UCP1 expression and increased oxygen consumption, respiratory uncoupling, norepinephrine-mediated thermogenesis, fatty acid oxidation and heat production, thus recapitulating the association between cold-induced FGF21 secretion and cold-induced thermogenesis in vivo.Conclusion:Beige adipocytes are thermogenic in humans. FGF21 is a beige adipokine capable of promoting a brown fat-like thermogenic program in WAs.Significance:This study provides first evidence of inducible functional thermogenic beige adipogenesis in human neck fat. FGF21 holds promise as a cold-induced beige adipokine with metabolic benefits of therapeutic relevance through browning of white adipose tissue.
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Cold-Activated Brown Adipose Tissue in Healthy Men
van Marken Lichtenbelt, W. D., Vanhommerig, J. W., Smulders, N. M., Drossaerts, J. M. A. F. L., Kemerink, G. J., Bouvy, N. D., Schrauwen, P., & Teule, G. J. J. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808718 · Cited by 3,452
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FGF-21 as a novel metabolic regulator
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Thermogenic Activation Induces FGF21 Expression and Release in Brown Adipose Tissue
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Cited by
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529
Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans
Lee, P., Linderman, J. D., Smith, S., Brychta, R. J., Wang, J., Idelson, C., Perron, R. M., Werner, C. D., Phan, G. Q., Kammula, U. S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.017 · Cited by 802
Self-citationTemperature-Acclimated Brown Adipose Tissue Modulates Insulin Sensitivity in Humans
Lee, P., Smith, S., Linderman, J., Courville, A. B., Brychta, R. J., Dieckmann, W., Werner, C. D., Chen, K. Y., & Celi, F. S. (2014) · Diabetes · doi:10.2337/db14-0513 · Cited by 398
Self-citationRuiz-Ojeda, F., Rupérez, A., Gomez-Llorente, C., Gil, A., & Aguilera, C. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17071040 · Cited by 375
Chen, K. Y., Cypess, A. M., Laughlin, M. R., Haft, C. R., Hu, H. H., Bredella, M. A., Enerbäck, S., Kinahan, P. E., Lichtenbelt, W. V. M., Lin, F. I., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.014 · Cited by 308
Metadata
- Authors
- Lee, P., Werner, C. D., Kebebew, E., & Celi, F. S.
- Venue
- International Journal of Obesity
- Published
- 2013-05-21
- Volume
- 38
- Issue
- 2
- Pages
- 170-176
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W2067641381
- Cited by
- 206
- References
- 11
- FWCI
- 20.81
- Type
- journal article
- Language
- en
- Open access
- bronze
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