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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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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