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FGF21 and the late adaptive response to starvation in humans
Open accessAbstract
In mice, FGF21 is rapidly induced by fasting, mediates critical aspects of the adaptive starvation response, and displays a number of positive metabolic properties when administered pharmacologically. In humans, however, fasting does not consistently increase FGF21, suggesting a possible evolutionary divergence in FGF21 function. Moreover, many key aspects of FGF21 function in mice have been identified in the context of transgenic overexpression or administration of supraphysiologic doses, rather than in a physiologic setting. Here, we explored the dynamics and function of FGF21 in human volunteers during a 10-day fast. Unlike mice, which show an increase in circulating FGF21 after only 6 hours, human subjects did not have a notable surge in FGF21 until 7 to 10 days of fasting. Moreover, we determined that FGF21 induction was associated with decreased thermogenesis and adiponectin, an observation that directly contrasts with previous reports based on supraphysiologic dosing. Additionally, FGF21 levels increased after ketone induction, demonstrating that endogenous FGF21 does not drive starvation-mediated ketogenesis in humans. Instead, a longitudinal analysis of biologically relevant variables identified serum transaminases--markers of tissue breakdown--as predictors of FGF21. These data establish FGF21 as a fasting-induced hormone in humans and indicate that FGF21 contributes to the late stages of adaptive starvation, when it may regulate the utilization of fuel derived from tissue breakdown.
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“Starvation30,31, high sugar intake32,33 and dietary protein restriction26 all induce circulating FGF21 levels in humans.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [31]
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“Consistent with data from rodents, circulating levels of FGF21 are also induced in humans during prolonged fasting (33, 42).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [33]
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Liu, X., Zhang, Y., Ma, C., Lin, J., & Du, J. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-07142-5 · Cited by 22
“Recently, seven to ten days of starvation is required for the circulating FGF21 concentration to increase in humans [36, 37], whereas fasting for up to 72 h does not change FGF21 levels [38, 39].”
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BackgroundMyokines: Novel therapeutic targets for diabetic nephropathy
Yang, M., Luo, S., Yang, J., Chen, W., He, L., Liu, D., Zhao, L., & Wang, X. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1014581 · Cited by 18
“The expression of FGF21 is mainly regulated by metabolic factors, including fasting (85), a high carbohydrate diet (86), and”
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Kerem, L., Holsen, L. M., Fazeli, P. K., Bredella, M. A., Mancuso, C., Resulaj, M., Holmes, T. M., Klibanski, A., & Lawson, E. A. (2020) · Physiological Reports · doi:10.14814/phy2.14639 · Cited by 16
“After a wash-out period, subjects were readmitted to the TCRC for a 10-day fast, using a validated protocol (Fazeli et al., 2015).”
MethodSelf-citationFibroblast growth factor 21 in dairy cows: current knowledge and potential relevance
Eder, K., Geßner, D. K., & Ringseis, R. (2021) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-021-00621-y · Cited by 18
“In contrast to mice, an elevation of blood FGF21 concentration in humans was observed only after a longer fasting period of at least 7 d, presumably due to the lower metabolic activity compared with mice [27, 28].”
BackgroundA Critical Assessment of Fasting to Promote Metabolic Health and Longevity
Fazeli, P. K., & Steinhauser, M. L. (2025) · Endocrine Reviews · doi:10.1210/endrev/bnaf021 · Cited by 19
“FGF21 is a hormone secreted predominantly by the liver with fasting (76, 85, 119).”
Self-citationDietary restriction in aging and longevity
Schmauck‐Medina, T., Lautrup, S., Francesco, A. D., Mitchell, S. J., Clemmensen, C., Partridge, L., Roth, G. S., Anderson, R. M., Mattison, J. A., de Cabo, R., et al. (2026) · Nature Aging · doi:10.1038/s43587-026-01091-5 · Cited by 18
Rasineni, K., Jordan, C. W., Thomes, P. G., Kubik, J. L., Staab, E. M., Sweeney, S. A., Talmon, G. A., Donohue, T. M., McNiven, M. A., Kharbanda, K. K., et al. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.625352 · Cited by 16
How Experiences Affect Psychological Responses During Supervised Fasting: A Preliminary Study
Ma, Q.-Y., Yang, C., Wu, R.-L., Wu, M., Liu, W., Dai, Z., & Li, Y.-H. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.651760 · Cited by 16
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“Additionally, the gene transcription of Fgf21 was reduced in the high phosphorus group compared to the adequate phosphorus group, which may also play a role in regulating muscle metabolism, as it has been shown to increase glucose uptake and utilization in muscle tissue [83]; a reduction would be in accordance with a…”
BackgroundEffects of dietary restriction on metabolic and cognitive health
Matos, M. S., Platt, B., & Delibegović, M. (2020) · Proceedings of The Nutrition Society · doi:10.1017/s0029665120007910 · Cited by 16
Epperlein, S., Gebhardt, C., Rohde, K., Chakaroun, R., Patt, M., Schamarek, I., Kralisch, S., Heiker, J. T., Scholz, M. R., Stümvoll, M., et al. (2021) · Biomedicines · doi:10.3390/biomedicines9040345 · Cited by 16
“, after acute exercising [3], longterm fasting [4], very low caloric diet [5], excessive intake of carbohydrates [6], in the postprandial period [7], after alcohol consumption [8], and lipid infusion [9], in type 2 diabetes (T2D) [10], metabolic syndrome (MS) and obesity [11,12].”
BackgroundResponse of skeletal muscle UCP2-expression during metabolic adaptation to caloric restriction
Heinitz, S., Piaggi, P., Yang, S., Bonfiglio, S. M., Steel, J., Krakoff, J. A., & Votruba, S. B. (2018) · International Journal of Obesity · doi:10.1038/s41366-018-0085-2 · Cited by 16
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“Although prolonged starvation in humans increases circulating FGF21 levels [33], it does not rise to normal levels in preterm infants with inadequate nutrition [30].”
BackgroundHron, B. M., Ebbeling, C. B., Feldman, H. A., & Ludwig, D. S. (2017) · Nutrition & Metabolism · doi:10.1186/s12986-017-0198-y · Cited by 15
“Owing to differences in assay type, the absolute values of FGF-21 in our study are lower than some published reports [26], yet consistent with more recent publications [27, 28].”
Result24-h severe energy restriction impairs postprandial glycaemic control in young, lean males
Clayton, D. J., Biddle, J., Maher, T., Funnell, M. P., Sargeant, J. A., King, J. A., Hulston, C. J., Stensel, D. J., & James, L. J. (2018) · British Journal Of Nutrition · doi:10.1017/s0007114518002568 · Cited by 14
“In contrast, human studies have observed no change in fasting or postprandial (OGTT) plasma FGF21 concentration after 16 h of fasting((45)), and one study found that it may take 7–10 d of fasting to elicit an increase in FGF21 in humans((46)).”
ResultFeng, J. N., Shao, W., & Jin, T. (2023) · Physiological Reports · doi:10.14814/phy2.15620 · Cited by 13
Hepatic function of glucagon-like peptide-1 and its based diabetes drugs
Feng, J. N., & Jin, T. (2024) · Medical Review · doi:10.1515/mr-2024-0018 · Cited by 17
Fiorenza, M., Checa, A., Sandsdal, R. M., Jensen, S. B. K., Juhl, C. R., Noer, M. H., Bogh, N. P., Lundgren, J. R., Janus, C., Stallknecht, B. M., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101629 · Cited by 14
“50 Conversely, we found a marked increase in serum GDF15 in response to the low-calorie diet (Figure 1C), corroborating prior data showing slight but significant increments following short-term ( % 8 weeks) calorie restriction.”
Stone, S., Wegner, D., Wambach, J., Cole, F. S., Urano, F., & Ornitz, D. M. (2020) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaa138 · Cited by 12
“FGF21 is a hormone primarily secreted by the liver that acts to regulate the body’s response to starvation through CNS and peripheral target tissues [12-14].”
BackgroundDomouzoglou, E. M., Vlahos, A. P., Cholevas, V., Papafaklis, M. I., Chaliasos, N., Siomou, E. C., Michalis, L. K., Tsatsoulis, A. A., & Naka, K. Κ. (2021) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2040258.129 · Cited by 12
“27) MS encompasses various metabolic deregulations such as dyslipidemia and insulin resistance as well as increased blood pressure and obesity, and FGF21 is a key protective molecule upregulated possibly due to overexpression to increase its effectiveness in such states.”
BackgroundLim, J. Y., & Kim, E. (2023) · Metabolites · doi:10.3390/metabo13090979 · Cited by 13
Xie, T., Yin, L., Guo, D., Zhang, Z., Chen, Y., Liu, B., Wang, W., & Zheng, Y. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119346 · Cited by 12
Brain-acting hepatokines: its impact on energy balance and metabolism
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Association of Glucagon to Insulin Ratio and Metabolic Syndrome in Patients with Type 2 Diabetes
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“Fibroblast growth factor 21 (FGF21) is a hormone produced by various tissues secreted in the fasting state and involved in metabolic responses to fasting [25].”
BackgroundMethionine as a regulator of bone remodeling with fasting
Amorim, T., Kumar, G. V. N., David, N. L., Dion, W. A., Pagadala, T., Doshi, N. K., Zhu, B., Parkhitko, A. A., Steinhauser, M. L., & Fazeli, P. K. (2024) · JCI Insight · doi:10.1172/jci.insight.177997 · Cited by 10
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“Changes in the body’s nutritional status, such as those induced by high-carbohydrate diets [39, 40], fasting or starvation [41, 42], or low-protein diets [43, 44], can affect its concentration.”
BackgroundXu, J., Zhang, R., Millischer, V., Stiernborg, M., Tume, C. E., Mehdinia, S., Barker, P., Yılmaz, Z., Gonçalves, V. F., Lavebratt, C., et al. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03425-0 · Cited by 10
“This despite that FGF21 expression is reported to be strongly induced by fasting [55] and protein restriction [56], and regulates energy homeostasis during starvation [55].”
Parsing the Potential Neuroendocrine Actions of FGF21 in Primates
Gillum, M. P. (2018) · Endocrinology · doi:10.1210/en.2018-00208 · Cited by 9
Arndt, M. B., Richardson, B. A., Mahfuz, M., Ahmed, T., Haque, R., Gazi, M. A., John-Stewart, G. C., Denno, D. M., Scarlett, J. M., & Walson, J. L. (2019) · Current Developments in Nutrition · doi:10.1093/cdn/nzz024 · Cited by 10
“FGF21 concentrations are hypothesized to be part of the late adaptive response to starvation, as serum FGF21 increases in healthy human adults after 7–10 d of fasting (16, 37).”
BackgroundPoloczek, J., Kazura, W., Kwaśnicka, E., Gumprecht, J., Jochem, J., & Stygar, D. M. (2021) · Journal of Diabetes Research · doi:10.1155/2021/5527107 · Cited by 10
“Fibroblast growth factor 21 (FGF-21) is a protein secreted by the liver [6] and induced in a fasting state [61].”
BackgroundLiu, J., Jiang, J., Li, Y., Chen, Q., Yang, T., Lei, Y., He, Z., Wang, X., Na, Q., Lao, C., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1439255 · Cited by 9
“Prolonged starvation, overnutrition, and glucagon all upregulated FGF21 expression (17 – 19), while insulin may inhibit FGF21 expression in the liver (20).”
BackgroundTh2 Cytokines Increase the Expression of Fibroblast Growth Factor 21 in the Liver
Kang, S., Lee, S. E., Choi, M., Chang, J.-Y., Kim, J.-T., Zhang, B., Kang, Y.-E., Lee, J. H., Yi, H., & Shong, M. (2021) · Cells · doi:10.3390/cells10061298 · Cited by 9
“Fgf21 mRNA expression was markedly increased in the liver after 6 h of fasting and was maintained over a 24-h fasting period [56].”
BackgroundFGF21 Normalizes Plasma Glucose in Mouse Models of Type 1 Diabetes and Insulin Receptor Dysfunction
Diener, J. L., Mowbray, S. F., Huang, W.-J., Yowe, D. L., Xu, J., Caplan, S. L., Misra, A., Kapur, A., Shapiro, J., Ke, X., et al. (2021) · Endocrinology · doi:10.1210/endocr/bqab092 · Cited by 9
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“And, in contrast to rodents, at least seven days of starvation are required for FGF21 levels to rise modestly (2-3 fold) ( Gälman et al., 2008 ; Fazeli et al., 2015 ), arguing against protein restriction or increased fatty acid delivery to the liver as major mechanisms for FGF21 production in…”
Huang, Y., Zhang, Y., Yang, N., Qian, Z., Fang, Z., Zeng, L., Huang, Y., Li, H., Luo, M., Yan, J., et al. (2024) · GeroScience · doi:10.1007/s11357-024-01463-y · Cited by 8
“For instance, cFGF21 levels are associated with fasting [4], protein restriction [5], carbohydrate levels [6], insulin resistance, and obesity [7].”
Self-citationSex Differences in Ketogenic Diet Response Reveal Gonadal Hormone Interaction With FGF21 in Mice
Zhang, Y., Cochran, J. D., Souvenir, R., Tai, W. C., Xia, R., Gladwin, B. S., Barton, N. B., Pereira, R. O., & Abel, E. D. (2025) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaf131 · Cited by 8
“These considerations could be further confounded by the effect of age, duration of diet, and the existence of other comorbidities [4-6, 9, 25].”
InfluentialSelf-citationFasting induces FGF21 in humans
Holmes, D. I. R. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.202 · Cited by 8
PTEN Deletion in Adult Mice Induces Hypoinsulinemia With Concomitant Low Glucose Levels
Crespo‐Masip, M., Pérez-Gómez, A., Guzmán, C., Rayego‐Mateos, S., Doladé, N. G., García-Carrasco, A., Jover, R., & Valdivielso, J. M. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.850214 · Cited by 8
“FGF21 is an adaptive response hormone to the late stages of starvation, when it may regulate the utilization of fuel derived from tissue breakdown (61).”
BackgroundUndernutrition and growth in the developing world
Nijjar, J. K., & Stafford, D. E. J. (2018) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000461 · Cited by 8
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Song, J., Hao, K., Chen, X., Zhang, Y., Cheng, Z., Mao, S., Tang, Y., Tong, X., & Dai, F. (2020) · Annals of Translational Medicine · doi:10.21037/atm.2020.01.18 · Cited by 6
“FGF21, as a stress hormone, has clear functions at the organism level in the maintenance of tissue homeostasis (18,19).”
BackgroundSelf-citationKang, C., & Avery, L. (2021) · Molecules and Cells · doi:10.14348/molcells.2021.0051 · Cited by 9
“In fact, recent studies suggest that FGF21 is a starvation-regulating hormone, which is induced under nutrient-deficient conditions and positively regulates a collection of starvation responses, such as growth inhibition, tissue breakdown, autophagy, and lipid degradation (Badman et al., 2007; Byun et al., 2020; Fazel…”
BackgroundInfluentialXie, W., Li, D., Shi, Y., Yu, N., Yan, Y.-M., Zhang, Y.-C., Yu, Q.-L., Li, Y., Du, J., Lin, Z.-F., et al. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.850517 · Cited by 5
“Previous studies indicated that FGF21 plays a key role in mediating the metabolic response to fasting/starvation by enhancing fatty acid oxidation, ketogenesis and inducing growth hormone resistance (10, 11).”
BackgroundSelf-citationCold exposure increases circulating fibroblast growth factor 21 in the evening in males and females
Hoekx, C. A., Martínez‐Téllez, B., Straat, M. E., Verkleij, M. M. A., Kemmeren, M., Kooijman, S., Uhrbom, M., de Jager, S. C. A., Rensen, P. C. N., & Boon, M. R. (2024) · Endocrine Connections · doi:10.1530/ec-24-0074 · Cited by 6
“While mice have a more pronounced and faster release of FGF21 upon cold exposure compared to humans, studies in humans have shown a significant increase in circulating FGF21 after fasting for 7–10 days and after prolonged exposure to mild cold for 10 days in men (19, 41, 42).”
BackgroundBranched chain amino acids prime metabolic inflammation
Doshi, N. K., Pesaresi, T., Pagadala, T., Dion, W. A., Zhang, Y., David, N. L., Amorim, T., Wang, W., Kumar, G. V. N., Zhu, B., et al. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102308 · Cited by 7
“In the present study, we leveraged our previously published longitudinal fasting dataset inclusive of metabolomics and clinical measures to uncover novel correlates to the inflammatory biomarker CRP [18 — 20].”
Self-citationDeBoer, M. D., Elwood, S., Platts-Mills, J. A., McDermid, J. M., Scharf, R. J., McQuade, E. T. R., Jatosh, S., Houpt, E. R., & Mduma, E. R. (2023) · Journal of Nutrition · doi:10.1016/j.tjnut.2023.03.020 · Cited by 6
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“Such chronic adaptive effects on FGF21 would accord with starvation models in humans whereby FGF21 elevations occur after ~7 days [22].”
BackgroundCarboo, J. A., Malan, L., Lombard, M. J., & Dolman, R. (2022) · Human Nutrition & Metabolism · doi:10.1016/j.hnm.2022.200181 · Cited by 6
Xu, L., Yu, H., Yin, J., Li, L., Zhou, J., Li, M., Li, Q., Chen, H., Liu, F., Bao, Y., et al. (2017) · Scientific Reports · doi:10.1038/srep43123 · Cited by 6
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“For instance, FGF21 is rapidly induced after 6 h of fasting in mice, but it is not upregulated until 7–10 days of starvation in human subjects [1,34].”
BackgroundCagigas, M. L., Santiappillai, N. T., Commissati, S., Fiorito, G., Masedunskas, A., Rajakumar, G., Ciutiis, I. D., Goldhamer, A. C., Kennedy, B. K., Hoy, A. J., et al. (2025) · Aging Cell · doi:10.1111/acel.70270 · Cited by 5
“In rodent models, fasting rapidly induces hepatic FGF21 to orchestrate the starvation response, whereas in humans, keto-genesis typically precedes any rise in FGF21 (Fazeli et al. 2015).”
Vankrunkelsven, W., Thiessen, S., Derde, S., Vervoort, E., Derese, I., Pintelon, I., Matheussen, H., Jans, A., Goossens, C., Langouche, L., et al. (2023) · Skeletal Muscle · doi:10.1186/s13395-023-00320-4 · Cited by 5
Sen, A., Youssef, S., Wendt, K., & Anakk, S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105322 · Cited by 6
Impact of Acutely Increased Endogenous- and Exogenous Ketone Bodies on FGF21 Levels in Humans
Lauritzen, E. S., Svart, M. V., Voss, T. S., Møller, N., & Bjerre, M. (2020) · Endocrine Research · doi:10.1080/07435800.2020.1831015 · Cited by 5
Moreno-Lopez, M., Louvet, I., Delalleau, N., Acosta-Montalvo, A., Thévenet, J., Pasquetti, G., Gmyr, V., Kerr-Conte, J. A., Pattou, F. N., Bonner, C., et al. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16089 · Cited by 4
UPRmt-regulated mitokines: novel strategies for myocardial injury repair
Gao, W., Liu, J., Zhang, W., Liu, B., & Shen, L. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1652353 · Cited by 4
Signals of energy availability in sleep: consequences of a fat-based metabolism
O’Hearn, L. A. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1397185 · Cited by 4
“FGF21 is more controversial in mechanism; there are mixed findings depending on species, tissue, and health of the subject (36–38).”
BackgroundQuaytman, J., David, N. L., Venugopal, S., Amorim, T., Beatrice, B., Toledo, F. G. S., Miller, R. G., Steinhauser, M. L., & Fazeli, P. K. (2024) · Contemporary Clinical Trials · doi:10.1016/j.cct.2024.107698 · Cited by 4
Self-citationCounteracting health risks by Modulating Homeostatic Signaling
Tian, J. J., Levy, M. A., Zhang, X., Sinnott, R., & Maddela, R. L. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106281 · Cited by 4
Circadian Regulation of Endocrine Fibroblast Growth Factors on Systemic Energy Metabolism
Yang, Z., Zarbl, H., & Guo, G. L. (2024) · Molecular Pharmacology · doi:10.1124/molpharm.123.000831 · Cited by 3
Valencia‐Ortega, J., Galicia-Hernández, V., Castillo-Santos, A., Molerés-Orduña, M., Arceo-Cerna, C., Perichart‐Perera, O., Rodríguez-Cano, A. M., Rodríguez-Hernández, C., Estrada‐Gutiérrez, G., Camacho‐Arroyo, I., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1423950 · Cited by 4
Budkowska, M., Ostrycharz, E., Cecerska‐Heryć, E., Dołęgowska, K., Siennicka, A., Nazarewski, Ł., Rykowski, P., & Dołęgowska, B. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26031299 · Cited by 3
Weight regain after bariatric surgery: Promoters and potential predictors
Demerdash, H. M. (2021) · World Journal of Meta-Analysis · doi:10.13105/wjma.v9.i5.438 · Cited by 3
Kalahasthi, R., Nagaraju, R., Balachandar, R., & Adepu, V. K. (2022) · Journal of Preventive Diagnostic and Treatment Strategies in Medicine · doi:10.4103/jpdtsm.jpdtsm_39_22 · Cited by 3
Zheng, P., Wang, F., Li, H., Chen, H., Li, M.-T., Ma, H., He, J., Chen, L., Liu, Y., & Xu, H. (2024) · Endocrine Connections · doi:10.1530/ec-24-0016 · Cited by 3
“We also measured levels of fibroblast growth factor 21 (FGF21), zinc, Cu, and iron in CSF. FGF21 is a metabolic cytokine involved in a plethora of tissue-specific effects ( 23, 24, 25, 26 ).”
BackgroundStarvation and fasting: Biochemical aspects
McGrath, K. H., Haller, W., & Bines, J. E. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821848-8.00068-8 · Cited by 3
Fluctuations of serum fibroblast growth factor-21 levels in prolonged fasting in male adults
Ağaçdiken, A., & Göktaş, Z. (2023) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2023.06.024 · Cited by 3
Zhang, X., Li, Z., Wang, S., & Chen, Y. (2025) · Nutrients · doi:10.3390/nu17071179 · Cited by 2
“In humans, Fgf21 expression can be induced by starvation [15,16], protein restriction [17], high-fructose or carbohydrate intake [18,19], and alcohol consumption [20,21].”
Fibroblast Growth Factor 21 as a Regulator of Energy Metabolism in the Liver and Adipose Tissue
Matikainen, N., & Söderlund, S. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816093-0.00013-6 · Cited by 2
Carboo, J. A., Malan, L., Lombard, M. J., Nienaber, A., & Dolman, R. (2024) · Cytokine · doi:10.1016/j.cyto.2024.156807 · Cited by 3
Multiomics unravels the complexity of male obesity: a prospective observational study
Papadakis, G. E., Favre, L., Zouaghi, Y., Vionnet, N., Niederländer, N. J., Adamo, M., Acierno, J. S., Berdous, D., Boizot, A., Meylan, J., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-024-06040-7 · Cited by 2
Fibroblast growth factor 21: new insights from human studies
Hansen, J. S., & Plomgaard, P. (2016) · Cardiovascular Endocrinology · doi:10.1097/xce.0000000000000084 · Cited by 2
Weissman, C., & Hashem, R. (2020) · Springer eBooks · doi:10.1007/978-3-030-39781-4_5 · Cited by 3
Bartmańska, M., Więcek, A., & Adamczak, M. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13144266 · Cited by 1
“This is associated with a reduction in thermogenesis and adiponectin, and does not stimulate starvation-induced ketogenesis [16].”
BackgroundElhusseiny, R., Ihsan, M., Labidi, M., Alhammoud, M., Mtibaa, K., Nader, N., Nasir, N., Farooq, A., Papakostas, E., Olory, B. C. R., et al. (2025) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003825 · Cited by 1
Gabriel, S., Ncube, M., Goldman, D., Scharf, E. L., Goldhamer, A. C., & Myers, T. R. (2025) · Obesity Science & Practice · doi:10.1002/osp4.70086 · Cited by 1
BOZKURT, A., Kara, E., Bulut, F. D., Kaplan, İ., Burgaç, E., Köşeci, B., Gündüz, N. T., Dağlıoğlu, G., Şeydaoğlu, G., Mungan, N. Ö., et al. (2025) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2025-0255 · Cited by 1
Efendi, O. G. H. N. B., Matsui, S., Tsukamoto, M., Oguri, Y., Tsuzuki, S., & Sasaki, T. (2025) · Bioscience Biotechnology and Biochemistry · doi:10.1093/bbb/zbaf147 · Cited by 1
Effect of Muscle Contraction Under Caloric Restriction on Irisin and FGF21 Secretion in Mice
Tanimura, R., Watanabe, H., Shirai, T., Uemichi, K., Iwata, T., & Takemasa, T. (2025) · Physiological Research · doi:10.33549/physiolres.935581 · Cited by 1
“Given that circulating FGF21 levels are highly responsive to both acute and chronic environmental and physiological factors [46,47], the decrease in serum FGF21 observed in the present study following CR may be attributable to variables such as pre-sampling fasting, animal age, and housing…”
Merrild, C., Johansen, V. B. I., Clemmensen, C., & Ranea‐Robles, P. (2026) · The Journal of Physiology · doi:10.1113/jp289817 · Cited by 1
Shen, Y., Chen, Q., Zhao, Z., Chen, Q., Tang, Y., Chen, F., Hao, T., Du, J., & Ai, Q. (2026) · The FASEB Journal · doi:10.1096/fj.202504683rr · Cited by 1
“As the pivotal organ in lipid metabolism, the liver responds to nutrient fluctuations by secreting hepatokines, which systemically orchestrate energy storage and utilization [1–3].”
Grandl, G., König, A., Metzger, F., Liśkiewicz, A., Hefele, T., Nason, S., Novikoff, A., Al-Refaie, N., Rahman, M. A., Khalil, A., et al. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2026.05.011 · Cited by 2
Higgins, C. B., Zhang, Y., Mayer, A. L., Fujiwara, H., Stothard, A. I., Graham, M. J., Swarts, B. M., & DeBosch, B. J. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/267781
Self-citationRôle des hépatokines dans le dialogue inter-organes en physiologie et physiopathologie
Pacheco, A., & Postic, C. (2020) · Médecine des Maladies Métaboliques · doi:10.1016/j.mmm.2020.04.008
Sen, A., Youssef, S., Wendt, K., & Anakk, S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.28.121632
“Since fibroblast growth factor receptor 1 (Fgfr1), fibroblast growth factor co-receptor β-Klotho, and fibroblast growth factor 21 (Fgf21) coordinate glucose and fat homeostasis (29-32), we examined their expression.”
BackgroundIntestinal-derived FGF15 preserves muscle and bone mass following sleeve gastrectomyPreprint
Bozadjieva-Kramer, N., Shin, J. H., Shao, Y., Gutiérrez‐Aguilar, R., Li, Z., Heppner, K. M., Chiang, S., Vargo, S. G., Granger, K., Sandoval, D. A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.02.130278
“, 2019) and reduced bone mineral density and BMAT (Bornstein et al., 2014; Fazeli et al., 2015; Wei et al., 2012).”
BackgroundAlliouachene, S., Kieswich, J. E., Bilanges, B., McCafferty, K., Thiemermann, C., Vanhaesebroeck, B., & Yaqoob, M. (2020) · American Journal of Transplantation · doi:10.1111/ajt.16470
The Growth Hormone-IGF-1 Axis in Anorexia Nervosa
Khiyami, A. M., & Fazeli, P. K. (2022) · Springer eBooks · doi:10.1007/978-3-030-67929-3_39-1
Self-citationThe Growth Hormone-IGF-1 Axis in Anorexia Nervosa
Khiyami, A. M., & Fazeli, P. K. (2023) · Springer eBooks · doi:10.1007/978-3-031-16691-4_39
Self-citationBond, S. T., King, E. J., Walker, S., Yang, C., Liu, Y., Liu, K. H., Zhuang, A., Jurrjens, A. W., Fang, H., Formosa, L. E., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.02.597064
Metadata
- Authors
- Fazeli, P. K., Lun, M., Kim, S. M., Bredella, M. A., Wright, S., Zhang, Y., Lee, H., Catana, C., Klibanski, A., Patwari, P., & Steinhauser, M. L.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Massachusetts General Hospital (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2015-11-03
- Volume
- 125
- Issue
- 12
- Pages
- 4601-4611
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC4665770
- OpenAlex
- W2155047676
- Cited by
- 214
- References
- 47
- Citations by year
- 2026: 9 · 2025: 25 · 2024: 21 · 2023: 14 · 2022: 26 · 2021: 23 · 2020: 28 · 2019: 16 · 2018: 22 · 2017: 13 · 2016: 16 · 2015: 1
- FWCI
- 7.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000170, UL1TR001102)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK094820, K08DK090147)
- National Institute of Biomedical Imaging and Bioengineering (P41EB015896)
- National Center for Research Resources (UL1RR025758)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- FGF21, fasting, starvation adaptation, human volunteers, thermogenesis, adiponectin, ketogenesis, transaminases, tissue breakdown, evolutionary divergence
- MeSH terms
- Adaptation, Physiological, Adult, Animals, Fasting, Female, Fibroblast Growth Factors, Humans, Male, Middle Aged, Starvation, Time Factors, Thermogenesis, Mice, Adiponectin
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