Hepatic FGF21 Expression Is Induced at Birth via PPARα in Response to Milk Intake and Contributes to Thermogenic Activation of Neonatal Brown Fat
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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: to protect against cold exposure via nonshivering thermogenesis and to burn excess calories and reduce fat accumulation.
“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]
Recent landmark studies have identified novel secreted proteins, such as liver FGF21, cardiac natriuretic peptides, and irisin, that stimulate brown adipocyte thermogenesis.
“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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Self-citationFGF21 reloaded: challenges of a rapidly growing field
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Self-citationMetabolic fibroblast growth factors (FGFs): Mediators of energy homeostasis
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- 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 › 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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