The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
FGF21 is an Akt‐regulated myokine
Open accessAbstract
Fibroblast growth factor‐21 (FGF21) functions as a metabolic regulator. The FGF21 transcript is reported to be abundantly expressed in liver, but little is known about the regulation of FGF21 expression in other tissues. In this study, we show that levels of FGF21 protein expression were similar in skeletal muscle and liver from fasted mice. FGF21 transcript and protein expression were upregulated in gastrocnemius muscle of skeletal muscle‐specific Akt1 transgenic mice. Serum concentration of FGF21 was also increased by Akt1 transgene activation. In cultured skeletal muscle cells, FGF21 expression and secretion was regulated by insulin, Akt transduction and LY294002. These data indicate that skeletal muscle is a source of FGF21 and that its expression is regulated by a phosphatidylinosistol 3‐kinase (PI3‐kinase)/Akt1 signaling pathway‐dependent mechanism.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Fibroblast growth factor-21 is regulated by insulin285 through the PI3K/Akt1 signaling pathway.286”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [286]
In the citing paper
“In skeletal muscle, FGF21 expression, in healthy conditions, is almost undetectable, and therefore, the circulating FGF21 is predominantly produced and released by the liver.6, 12”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [6]
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 [6]
In the citing paper
“Recent studies reported that skeletal muscle is not only a producer but also a target of FGF21 because it expresses the cofactor β‐klotho and the FGFRs.6, 13, 14, 17, 18, 19”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [6]
In the citing paper
“In contrast, muscle‐dependent systemic release of FGF21 increases with starvation, endoplasmic reticulum stress, mitochondrial dysfunction, obesity, mitochondrial myopathies, and aging.6, 13, 14, 15, 16, 17, 18, 19”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [6]
In the citing paper
“In skeletal muscle, FGF21 expression, in healthy conditions, is almost undetectable, and therefore, the circulating FGF21 is predominantly produced and released by the liver.6, 12”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [6]
In the citing paper
“(ii) FGF21 is a stress‐induced myokine, which is released under conditions of starvation, ER stress, mitochondrial dysfunction, obesity, mitochondrial myopathies, and aging.6, 13, 14, 15, 16, 17, 18”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [6]
In the citing paper
“For example, FGF21 production from skeletal muscle (56, 61, 103, 128), BAT (59), and cardiac tissue (143) is increased in genetic mouse models of cellular or mitochondrial stress.”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [56]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Cellular survival: a play in three Akts
Datta, S. R., Brunet, A., & Greenberg, M. E. (1999) · Genes & Development · doi:10.1101/gad.13.22.2905 · Cited by 4,216
Bodine, S. C., Stitt, T. N., Gonzalez, M., Kline, W. O., Stover, G. L., Bauerlein, R., Zlotchenko, E., Scrimgeour, A., Lawrence, J. C., Glass, D. J., et al. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-1014 · Cited by 2,752
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
Self-citationInagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504
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
HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α
Arany, Z., Foo, S.-Y., Ma, Y., Ruas, J. L., Bommi-Reddy, A., Girnun, G., Cooper, M., Laznik, D., Chinsomboon, J., Rangwala, S. M., et al. (2008) · Nature · doi:10.1038/nature06613 · Cited by 1,054
Shiojima, I. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24682 · Cited by 935
Identification of a novel FGF, FGF-21, preferentially expressed in the liver
Nishimura, T., Nakatake, Y., Konishi, M., & Itoh, N. (2000) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(00)00067-1 · Cited by 847
Role of Myokines in Exercise and Metabolism
Pedersen, B. K., Åkerström, T. C. A., Nielsen, A. R., & Fischer, C. P. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00080.2007 · Cited by 841
The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21
Kharitonenkov, A., Wroblewski, V. J., Koester, A., Chen, Y.-F., Clutinger, C. K., Tigno, X. T., Hansen, B. C., Shanafelt, A. B., & Etgen, G. J. (2007) · Endocrinology · doi:10.1210/en.2006-1168 · Cited by 738
Self-citationGälman, C., Lundåsen, T., Kharitonenkov, A., Bina, H. A., Eriksson, M., Hafström, I., Dahlin, M., Åmark, P., Angelin, B., & Rudling, M. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.06.014 · Cited by 512
Self-citationWente, W., Efanov, A. M., Brenner, M. B., Kharitonenkov, A., Koster, A. M., Sandusky, G. E., Sewing, S., Treinies, I., Zitzer, H., & Gromada, J. (2006) · Diabetes · doi:10.2337/db05-1435 · Cited by 497
Self-citationAtherton, P. J., Babraj, J. A., Smith, K., Singh, J., Rennie, M. J., & Wackerhage, H. (2005) · The FASEB Journal · doi:10.1096/fj.04-2179fje · Cited by 475
Conditional Activation of Akt in Adult Skeletal Muscle Induces Rapid Hypertrophy
Lai, K.-M. V., Gonzalez, M., Poueymirou, W. T., Kline, W. O., Na, E., Zlotchenko, E., Stitt, T. N., Economides, A. N., Yancopoulos, G. D., & Glass, D. J. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.21.9295-9304.2004 · Cited by 442
Fast/Glycolytic Muscle Fiber Growth Reduces Fat Mass and Improves Metabolic Parameters in Obese Mice
Izumiya, Y., Hopkins, T., Morris, C., Sato, K., Zeng, L., Viereck, J., Hamilton, J. A., Ouchi, N., LeBrasseur, N. K., & Walsh, K. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.003 · Cited by 395 · cited 6×
“IIb, but not type I or IIa, muscle and the upregulation of glycolytic pathways, whereas oxidative pathways are decreased [17].”
BackgroundMethodInfluentialSelf-citationIntracellular signaling specificity in skeletal muscle in response to different modes of exercise
Nader, G. A., & Esser, K. A. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.90.5.1936 · Cited by 372
PPARα is a key regulator of hepatic FGF21
Lundåsen, T., Hunt, M., Nilsson, L.-M., Sanyal, S., Angelin, B., Alexson, S., & Rudling, M. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.06.068 · Cited by 361
Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathwayPreprint
Shiojima, I., & Walsh, K. X. (2006) · Genes & Development · doi:10.1101/gad.1492806 · Cited by 357
Self-citationMuise, E. S., Azzolina, B., Kuo, D. W., El-Sherbeini, M., Tan, Y., Yuan, X., Mu, J., Thompson, J. R., Berger, J. P., & Wong, K. K. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.044826 · Cited by 294
Bolster, D. R., Kubica, N., Crozier, S. J., Williamson, D. L., Farrell, P. A., Kimball, S. R., & Jefferson, L. S. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.047019 · Cited by 253
Ouchi, N., Shibata, R., & Walsh, K. X. (2005) · Circulation Research · doi:10.1161/01.res.0000163633.10240.3b · Cited by 244
Self-citationFGF21 attenuates lipolysis in human adipocytes – A possible link to improved insulin sensitivity
Arner, P., Pettersson, A., Mitchell, P. J., Dunbar, J. D., Kharitonenkov, A., & Rydén, M. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.04.038 · Cited by 234
Self-citationPedersen, B. K., & Febbraio, M. (2005) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2005.04.008 · Cited by 233
Molecular determinants of FGF‐21 activity—synergy and cross‐talk with PPARγ signaling
Moyers, J. S., Shiyanova, T. L., Mehrbod, F., Dunbar, J. D., Noblitt, T. W., Otto, K. A., Reifel-Miller, A. E., & Kharitonenkov, A. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20847 · Cited by 193
Self-citationWang, H., Qiang, L., & Farmer, S. R. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00992-07 · Cited by 181
Myogenic Akt Signaling Regulates Blood Vessel Recruitment during Myofiber Growth
Takahashi, A., Kureishi, Y., Jiang, Y., Luo, Z., Guo, K. Y., Mukhopadhyay, D., Ivashchenko, Y., Branellec, D., & Walsh, K. X. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.13.4803-4814.2002 · Cited by 157
Self-citationShield, M. A., Haugen, H. S., Clegg, C. H., & Hauschka, S. D. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.5058 · Cited by 115
Fibroblast Growth Factor-21 as a Therapeutic Agent for Metabolic Diseases
Kharitonenkov, A., & Shanafelt, A. B. (2008) · BioDrugs · doi:10.2165/00063030-200822010-00004 · Cited by 98
Self-citationKrzysik-Walker, S. M., Ocón-Grove, O. M., Maddineni, S. R., Hendricks, G. L., & Ramachandran, R. (2007) · Endocrinology · doi:10.1210/en.2007-1301 · Cited by 91
Schiekofer, S., Shiojima, I., Sato, K., Galasso, G., Oshima, Y., & Walsh, K. X. (2006) · Physiological Genomics · doi:10.1152/physiolgenomics.00234.2005 · Cited by 53
Self-citationGrill, M. A., Bales, M. A., Fought, A. N., Rosburg, K. C., Munger, S. J., & Antin, P. B. (2003) · Transgenic Research · doi:10.1023/a:1022119005836 · Cited by 32
Flagged first, then by citations
Research works printed but not linked: 1
- Wang H., 2007, Identification of a domain within PPAR gamma regulating expression of a group of genes containing FGF21 that are selectively repressed by SIRT1 in adipocytes, Mol. Cell Biol.
Cited by
Sorted by citations
Muscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909
The FGF family: biology, pathophysiology and therapy
Beenken, A., & Mohammadi, M. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2792 · Cited by 1,945
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529
Pancreatic regulation of glucose homeostasis.
Röder, P. V., Wu, B., Liu, Y., & Han, W. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.6 · Cited by 985
Rao, R. R., Long, J. Z., White, J. P., Svensson, K. J., Lou, J., Lokurkar, I., Jedrychowski, M. P., Ruas, J. L., Wrann, C. D., Lo, J. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.065 · Cited by 973
Metadata
- Authors
- Izumiya, Y., Bina, H. A., Ouchi, N., Akasaki, Y., Kharitonenkov, A., & Walsh, K.
- Affiliations
- Boston University (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Walsh, Kenneth
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2008-10-21
- Volume
- 582
- Issue
- 27
- Pages
- 3805-3810
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- PMC
- PMC2604129
- OpenAlex
- W2047726905
- Cited by
- 415
- References
- 31
- Citations by year
- 2026: 7 · 2025: 23 · 2024: 25 · 2023: 25 · 2022: 21 · 2021: 18 · 2020: 20 · 2019: 35 · 2018: 31 · 2017: 26 · 2016: 21 · 2015: 36 · 2014: 33 · 2013: 23 · 2012: 24
- FWCI
- 6.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG015052, R37AG015052, AG15052)
- National Heart, Lung, and Blood Institute (HL81587, HL77774, R01HL086785, P01HL081587, HL 86785, R01HL077774)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- FGF21, myokines, AKT1, skeletal muscle, PI3K/Akt signaling, insulin, gastrocnemius, metabolic regulation, fasting
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Animals, Cell Line, Chromones, Fibroblast Growth Factors, Insulin, Liver, Mice, Transgenic, Morpholines, Signal Transduction, Up-Regulation, Muscle, Skeletal, Phosphatidylinositol 3-Kinases, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
