The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Hepatic FGF21 Expression Is Induced at Birth via PPARα in Response to Milk Intake and Contributes to Thermogenic Activation of Neonatal Brown Fat
Open accessAbstract
Plasma FGF21 levels and hepatic FGF21 gene expression increase dramatically after birth in mice. This induction is initiated by suckling, requires lipid intake, is impaired in PPARalpha null neonates, and is mimicked by treatment with the PPARalpha activator, Wy14,643. Neonates exhibit reduced FGF21 expression in response to fasting, in contrast to the upregulation occurring in adults. Changes in FGF21 expression due to suckling or nutritional manipulations were associated with circulating free fatty acid and ketone body levels. We mimicked the FGF21 postnatal rise by injecting FGF21 into fasting neonates, and found that this enhanced the expression of genes involved in thermogenesis within brown fat, and increased body temperature. Brown adipocytes treated with FGF21 exhibited increased expression of thermogenic genes, higher total and uncoupled respiration, and enhanced glucose oxidation. We propose that the induction of FGF21 production by the liver mediates direct activation of brown fat thermogenesis during the fetal-to-neonatal transition.
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“In rodents, BAT generates heat mainly for two reasons; namely, to protect against cold exposure *via* nonshivering thermogenesis and to burn the excess calories and reduce fat accumulation ([54](#B54), [72](#B72)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [72]
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“Recent landmark studies have identified novel secreted proteins, such as liver FGF21 ([72](#B72)), cardiac natriuretic peptides ([11](#B11)), and irisin ([12](#B12)), that stimulate brown adipocyte thermogenesis.”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [72]
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FGF-21 as a novel metabolic regulator
Kharitonenkov, A., Shiyanova, T. L., Koester, A., Ford, A. M., Micanovic, R., Galbreath, E. J., Sandusky, G. E., Hammond, L. J., Moyers, J. S., Owens, R. A., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23606 · Cited by 2,125
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Badman, M. K., Pissios, P., Kennedy, A. R., Koukos, G., Flier, J. S., & Maratos-Flier, E. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.002 · Cited by 1,495
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Fibroblast Growth Factor 21 Corrects Obesity in Mice
Coskun, T., Bina, H. A., Schneider, M. A., Dunbar, J. D., Hu, C. C., Chen, Y., Moller, D. E., & Kharitonenkov, A. (2008) · Endocrinology · doi:10.1210/en.2008-0816 · Cited by 1,031
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Potthoff, M. J., Inagaki, T., Satapati, S., Ding, X., He, T., Goetz, R., Mohammadi, M., Finck, B. N., Mangelsdorf, D. J., Kliewer, S. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904187106 · Cited by 704
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Chavez, A. O., Molina-Carrion, M., Abdul-Ghani, M. A., Folli, F., DeFronzo, R. A., & Tripathy, D. (2009) · Diabetes Care · doi:10.2337/dc09-0684 · Cited by 390
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Cited by
Sorted by citations
Brown and beige fat: Development, function and therapeutic potential
Harms, M., & Seale, P. (2013) · Nature Medicine · doi:10.1038/nm.3361 · Cited by 2,328
FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis
Fisher, F. M., Kleiner, S., Douris, N., Fox, E. C., Mepani, R. J., Verdeguer, F., Wu, J., Kharitonenkov, A., Flier, J. S., Maratos-Flier, E., et al. (2012) · Genes & Development · doi:10.1101/gad.177857.111 · Cited by 1,478
Adipose tissue browning and metabolic health
Bartelt, A., & Heeren, J. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.204 · Cited by 1,177
Understanding the Physiology of FGF21
Fisher, F. M., & Maratos-Flier, E. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105339 · Cited by 912
Adaptive thermogenesis in adipocytes: Is beige the new brown?
Wu, J., Cohen, P., & Spiegelman, B. M. (2013) · Genes & Development · doi:10.1101/gad.211649.112 · Cited by 828
Metadata
- Authors
- Hondares, E., Rosell, M., Gonzalez, F. J., Giralt, M., Iglesias, R., & Villarroya, F.
- Affiliations
- Centro de Investigación Biomédica en Red (ES)
- National Cancer Institute (US)
- Corresponding author
- Villarroya, Francesc
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 11
- Issue
- 3
- Pages
- 206-212
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2847690
- OpenAlex
- W1988869711
- Cited by
- 377
- References
- 18
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 10 · 2023: 16 · 2022: 16 · 2021: 13 · 2020: 23 · 2019: 17 · 2018: 27 · 2017: 25 · 2016: 29 · 2015: 37 · 2014: 34 · 2013: 41 · 2012: 36
- FWCI
- 13.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (ZIABC005708)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- FGF21, PPARα, thermogenesis, suckling, milk consumption, dietary fat intake, ketone bodies, free fatty acids, neonatal transition, hepatic gene expression, brown adipocytes, uncoupled respiration, glucose oxidation, fasting, Wy-14,643
- MeSH terms
- Animals, Animals, Newborn, Animals, Suckling, Blood Glucose, Body Temperature, Adipose Tissue, Brown, Fasting, Fatty Acids, Fibroblast Growth Factors, Ketone Bodies, Liver, Milk, Respiration, Up-Regulation, Glucose Intolerance, Mice, Knockout, Thermogenesis, PPAR alpha, Mice, Adipocytes, Brown
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