The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Endocrine Regulation of the Fasting Response by PPARα-Mediated Induction of Fibroblast Growth Factor 21
Open accessAbstract
Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the utilization of fat as an energy source during starvation and is the molecular target for the fibrate dyslipidemia drugs. Here, we identify the endocrine hormone fibroblast growth factor 21 (FGF21) as a mediator of the pleiotropic actions of PPARalpha. FGF21 is induced directly by PPARalpha in liver in response to fasting and PPARalpha agonists. FGF21 in turn stimulates lipolysis in white adipose tissue and ketogenesis in liver. FGF21 also reduces physical activity and promotes torpor, a short-term hibernation-like state of regulated hypothermia that conserves energy. These findings demonstrate an unexpected role for the PPARalpha-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation.
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In the citing paper
“In WAT, it induces lipolysis [166] and browning [43], likely via upregulation of PGC-1α [192].”
The cited source says what the claim attributes to it.
In the citing paper
“While both FGF21 [166] and ANGPTL4 [176,177] induce WAT lipolysis (4)”
In the citing paper
“The metabolic regulator FGF21 is expressed and released into the general circulation by several tissues such as the liver, WAT, BAT, and the heart.7, 8, 9, 10, 11”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [8]
In the citing paper
“Starvation is one of the stress conditions known to induce FGF21 expression in the liver,8, 32 WAT,10 and skeletal muscle (Figure 2A).6”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [8]
In the citing paper
“FGF21 was initially proposed to be a late-fasting/starvation factor, because it is transcriptionally induced during extended fasting, through a mechanism dependent on the transcription factor PPARα, and it regulates the adaptive fasting response20,21.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [20]
In the citing paper
“Classically recognized as a fasting hormone regulated by the nuclear receptor peroxisome proliferator-activated receptor α (PPARα) [150,151]”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [151]
In the citing paper
“The Fgf21 promoter contains PPARα response elements that lead to the induction of hepatic and circulating levels of FGF21 during prolonged fasting (54).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [54]
In the citing paper
“Multiple groups discovered that PPARα-mediated induction of FGF21 is important for the adaptive fasting response (7, 54).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [54]
In the citing paper
“In rodents, pharmacological levels of FGF21 increase energy expenditure (64, 141), which results in increased food intake (54, 64).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [54]
In the citing paper
“Fibroblast growth factor 21 (FGF21) was first identified as an hepatokine 61 and has been shown to be necessary for the adaptation to fasting 62, 63.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [63]
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Citations
Cites
A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189
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
Roles of PPARs in health and disease
Kersten, S., Desvergne, B., & Wahli, W. (2000) · Nature · doi:10.1038/35013000 · Cited by 1,956
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., Richardson, J. A., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.09.001 · Cited by 1,865
Self-citationPeroxisome proliferator–activated receptor α mediates the adaptive response to fasting
Kersten, S., Seydoux, J., Peters, J. M., Gonzalez, F. J., Desvergne, B., & Wahli, W. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6223 · Cited by 1,649
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
Cahill, G. F. (2006) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.26.061505.111258 · Cited by 1,360
Metabolic Rate and Body Temperature Reduction During Hibernation and Daily Torpor
Geiser, F. (2004) · Annual Review of Physiology · doi:10.1146/annurev.physiol.66.032102.115105 · Cited by 1,153
Evolution of the Fgf and Fgfr gene families.
Itoh, N., & Ornitz, D. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.08.007 · Cited by 1,123
Sorting out the roles of PPAR in energy metabolism and vascular homeostasis
Lefebvre, P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27989 · Cited by 962
Cited by
Sorted by citations
The Fibroblast Growth Factor signaling pathway
Ornitz, D. M., & Itoh, N. (2015) · WIREs Developmental Biology · doi:10.1002/wdev.176 · Cited by 2,050
The FGF family: biology, pathophysiology and therapy
Beenken, A., & Mohammadi, M. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2792 · Cited by 1,945
Self-citationBadman, 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
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
Homeostasis, Inflammation, and Disease Susceptibility
Kotas, M. E., & Medzhitov, R. (2015) · Cell · doi:10.1016/j.cell.2015.02.010 · Cited by 1,213
Metadata
- Authors
- Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., Elmquist, J. K., Gerard, R. D., Burgess, S. C., Hammer, R. E., Mangelsdorf, D. J., & Kliewer, S. A.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Van Andel Institute (US)
- New York University (US)
- Corresponding author
- Kliewer, Steven A.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 5
- Issue
- 6
- Pages
- 415-425
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2119331212
- Cited by
- 1,504
- References
- 53
- Citations by year
- 2026: 42 · 2025: 66 · 2024: 59 · 2023: 78 · 2022: 113 · 2021: 102 · 2020: 80 · 2019: 94 · 2018: 89 · 2017: 99 · 2016: 106 · 2015: 101 · 2014: 92 · 2013: 74 · 2012: 94
- FWCI
- 21.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- American Diabetes Association
- Richard and Susan Smith Family Foundation
- GlaxoSmithKline
- University of Texas Southwestern Medical Center
- University of Pittsburgh
- National Institutes of Health (DK53301, U19DK62434)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK53301, DK-067158, U19 DK-62434, U24DK076169, U19DK062434, R01DK067158)
- National Institute of Dental and Craniofacial Research (DE13686, R01DE013686)
- National Center for Research Resources (P20RR20691, P20RR020691)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- PPARα, FGF21, fasting response, starvation, hormone signaling, lipolysis, white adipose tissue, ketogenesis, liver, physical activity, torpor, energy conservation
- MeSH terms
- Adenoviridae, Adipose Tissue, Animals, Cells, Cultured, Fasting, Female, Fibroblast Growth Factors, Humans, Lipolysis, Liver, Male, Mice, Inbred C57BL, Mice, Transgenic, Plasmids, RNA, Messenger, Transfection, Immunoblotting, Signal Transduction, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Hepatocytes, Chromatin Immunoprecipitation, PPAR alpha, Mice
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