Circulating Fibroblast Growth Factor 21 Is Induced by Peroxisome Proliferator-Activated Receptor Agonists But Not Ketosis in Man
Abstract
CONTEXT: Murine fibroblast growth factor (FGF) 21 is a nutritionally regulated hormone secreted by the liver principally in response to peroxisome proliferator-activated receptor-alpha (PPAR alpha) activation, which plays a critical role in regulating metabolism during ketosis. FGF21 is also a PPAR gamma target gene in mouse adipose tissue. Little information is available on FGF21 functions in humans. OBJECTIVE: The aim of the study was to measure plasma FGF21 during fasting, ketogenic diet, and PPAR agonist treatment in humans. DESIGN AND SETTING: We conducted a prospective study involving three patient groups at two university hospitals. PATIENTS: Eight healthy male volunteers underwent a 48-h period of starvation followed by 24-h refeeding (group 1); seven obese individuals were allocated to a low-carbohydrate diet for 3 months (group 2); and three groups of healthy, overweight or obese male volunteers received treatment with a PPAR alpha (20 microg/d GW590735) (n=6), PPAR delta (10 mg/d GW501516) (n=6), or PPAR gamma agonist (rosiglitazone) (n=10) for 2 wk (group 3). MAIN OUTCOME MEASURES: Fasting plasma FGF21 and serum 3-hydroxybutyrate were measured. RESULTS: There was no significant variation in human plasma FGF21 during fasting and refeeding. A 3-month ketogenic diet was associated with a 42% decline in plasma FGF21 levels. Circulating FGF21 increased significantly in response to treatment with PPAR alpha (39%) and PPAR delta (32%), but not PPAR gamma agonists. CONCLUSION: FGF21 does not play a major role in regulating the fasting response or ketosis in man. However, plasma FGF21 is elevated in response to pharmacological activation of PPAR alpha and PPAR delta and may contribute to the beneficial metabolic effects observed in response to pharmacotherapy with these compounds.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Ketogenic diets do not induce plasma FGF21 levels in humans.
“ketogenic diets do not induce plasma FGF21 levels in humans26,30,34”
From Metabolic messengers: FGF21 (2021) · cites this paper as [34]
Circulating FGF21 levels fail to increase in humans in response to a ketogenic diet.
“Importantly, it is unclear whether there is any translational relevance of FGF21 to the beneficial effects of ketogenic diets in humans because circulating FGF21 levels fail to increase in humans in response to a ketogenic diet (19, 42, 73).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [19]
The effect of fasting and ketogenic diets to increase FGF21 is not nearly as robust in humans as initially observed in mice.
“The effect of fasting and ketogenic diets to increase FGF21 is not nearly as robust in humans as initially observed in mice”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [131]
Cites
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 · see citing works
Inagaki, 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 · see citing works
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 · see citing works
Xu, J., Lloyd, D. J., Hale, C., Stanislaus, S., Chen, M., Sivits, G., Vonderfecht, S., Hecht, R., Li, Y.-S., Lindberg, R. A., et al. (2009) · Diabetes · doi:10.2337/db08-0392 · Cited by 1,151 · see citing works
Fibroblast Growth Factor 21 Corrects Obesity in Mice
Coskun, T., Bina, H. A., Schneider, M. A., Dunbar, J. D., Hu, C. C., Chen, Y., Moller, D. E., & Kharitonenkov, A. (2008) · Endocrinology · doi:10.1210/en.2008-0816 · Cited by 1,031 · see citing works
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 · see citing works
Zhang, X., Yeung, D. C. Y., Karpisek, M., Stejskal, D., Zhou, Z.-G., Liu, F., Wong, R. L. C., Chow, W.-S., Tso, A. W. K., Lam, K. S. L., et al. (2008) · Diabetes · doi:10.2337/db07-1476 · Cited by 908 · see citing works
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 · see citing works
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 · see citing works
PPAR : a dagger in the heart of the metabolic syndrome
Barish, G. D. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27955 · Cited by 641 · see citing works
βKlotho is required for metabolic activity of fibroblast growth factor 21
Ogawa, Y., Kurosu, H., Yamamoto, M., Nandi, A., Rosenblatt, K. P., Goetz, R., Eliseenkova, A. V., Mohammadi, M., & Kuro-o, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701600104 · Cited by 617 · see citing works
Gälman, 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 · see citing works
Wente, 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 · see citing works
FGF21 is an Akt‐regulated myokine
Izumiya, Y., Bina, H. A., Ouchi, N., Akasaki, Y., Kharitonenkov, A., & Walsh, K. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.10.021 · Cited by 415 · see citing works
Functional evolutionary history of the mouse Fgf gene family
Itoh, N., & Ornitz, D. M. (2007) · Developmental Dynamics · doi:10.1002/dvdy.21388 · Cited by 409 · see citing works
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 · see citing works
Suzuki, M., Uehara, Y., Motomura-Matsuzaka, K., Oki, J., Koyama, Y., Kimura, M., Asada, M., Komi-Kuramochi, A., Oka, S., & Toru, T. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0313 · Cited by 345 · see citing works
FGF‐21/FGF‐21 receptor interaction and activation is determined by βKlotho
Kharitonenkov, A., Dunbar, J. D., Bina, H. A., Bright, S. W., Moyers, J. S., Zhang, C., Ding, L., Micanovic, R., Mehrbod, S. F., Knierman, M. D., et al. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21357 · Cited by 329 · see citing works
Risérus, U., Sprecher, D. L., Johnson, T., Olson, E., Hirschberg, S., Liu, A., Fang, Z., Hegde, P. S., Richards, D. B., Sarov-Blat, L., et al. (2007) · Diabetes · doi:10.2337/db07-1318 · Cited by 326 · see citing works
Self-citationIto, S., Kinoshita, S., Shiraishi, N., Nakagawa, S., Sekine, S., Fujimori, T., & Nabeshima, Y. (2000) · Mechanisms of Development · doi:10.1016/s0925-4773(00)00439-1 · Cited by 312 · see citing works
Muise, 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 · see citing works
Wang, H., Qiang, L., & Farmer, S. R. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00992-07 · Cited by 181 · see citing works
Tsintzas, K., Jewell, K., Kamran, M., Laithwaite, D., Boonsong, T., Littlewood, J. J., Macdonald, I. A., & Bennett, A. J. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.109892 · Cited by 111 · see citing works
Self-citationPlasma Concentrations of Fibroblast Growth Factors 19 and 21 in Patients with Anorexia Nervosa
Dostálová, I., Kaválková, P., Haluzíková, D., Lacinová, Z., Mráz, M., Papežová, H., & Haluzı́k, M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0746 · Cited by 111 · see citing works
Li, H., Bao, Y., Xu, A., Pan, X., Lu, J., Wu, H., Lu, H., Xiang, K., & Jia, W. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2331 · Cited by 108 · see citing works
Dyson, P. A., Beatty, S. J., & Matthews, D. R. (2007) · Diabetic Medicine · doi:10.1111/j.1464-5491.2007.02290.x · Cited by 105 · see citing works
Self-citationCircadian expression of FGF21 is induced by PPARα activation in the mouse liver
Oishi, K., Uchida, D., & Ishida, N. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.09.046 · Cited by 95 · see citing works
Flagged first, then by citations
17 of the 45 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Understanding the Physiology of FGF21
Fisher, F. M., & Maratos-Flier, E. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105339 · Cited by 912 · see citing works
PPARs in Obesity-Induced T2DM, Dyslipidaemia and NAFLD
Gross, B., Pawlak, M., Lefebvre, P., & Staels, B. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.135 · Cited by 778 · see citing works
The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic
Geng, L., Lam, K. S. L., & Xu, A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0386-0 · Cited by 607 · see citing works
Increased Fibroblast Growth Factor 21 in Obesity and Nonalcoholic Fatty Liver Disease
Dushay, J., Chui, P. C., Gopalakrishnan, G. S., Varela–Rey, M., Crawley, M., Fisher, F. M., Badman, M. K., Martinez–Chantar, M. L., & Maratos–Flier, E. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.04.054 · Cited by 607 · see citing works
FGF21 is an endocrine signal of protein restriction
Laeger, T., Henagan, T. M., Albarado, D. C., Redman, L. M., Bray, G. A., Noland, R. C., Münzberg, H., Hutson, S. M., Gettys, T. W., Schwartz, M. W., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74915 · Cited by 593 · see citing works
Dutchak, P. A., Katafuchi, T., Bookout, A. L., Choi, J. H., Yu, R. T., Mangelsdorf, D. J., & Kliewer, S. A. (2012) · Cell · doi:10.1016/j.cell.2011.11.062 · Cited by 537 · see citing works
Mardinoğlu, A., Wu, H., Björnson, E., Zhang, C., Hakkarainen, A., Räsänen, S., Lee, S., Mancina, R. M., Bergentall, M., Pietiläinen, K. H., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.01.005 · Cited by 455 · see citing works
Endocrine fibroblast growth factors 15/19 and 21: from feast to famine
Potthoff, M. J., Kliewer, S. A., & Mangelsdorf, D. J. (2012) · Genes & Development · doi:10.1101/gad.184788.111 · Cited by 442 · see citing works
Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23
Degirolamo, C., Sabbà, C., & Moschetta, A. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.9 · Cited by 424 · see citing works
Li, H., Fang, Q., Gao, F., Fan, J., Zhou, J., Wang, X., Zhang, H., Pan, X., Bao, Y., Xiang, K., et al. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.05.018 · Cited by 400 · see citing works
Flippo, K. H., & Potthoff, M. J. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00354-2 · Cited by 311 · see citing works
Tissue-specific actions of the metabolic hormones FGF15/19 and FGF21
Owen, B. M., Mangelsdorf, D. J., & Kliewer, S. A. (2015) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2014.10.002 · Cited by 286 · see citing works
Fibroblast Growth Factor 21—Metabolic Role in Mice and Men
Staiger, H., Keuper, M., Berti, L., Hrabě de Angelis, M., & Häring, H.-U. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00016 · Cited by 270 · see citing works
Fructose ingestion acutely stimulates circulating FGF21 levels in humans
Dushay, J. R., Toschi, E., Mitten, E. K., Fisher, F. M., Herman, M. A., & Maratos-Flier, E. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2014.09.008 · Cited by 233 · see citing works
Mashili, F. L., Austin, R. L., Deshmukh, A. S., Fritz, T., Caidahl, K., Bergdahl, K., Zierath, J. R., Chibalin, A., Moller, D. E., Kharitonenkov, A., et al. (2011) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.1177 · Cited by 222 · see citing works
Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis
BonDurant, L. D., & Potthoff, M. J. (2018) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064800 · Cited by 222 · see citing works
Ehrenborg, E., & Krook, A. (2009) · Pharmacological Reviews · doi:10.1124/pr.109.001560 · Cited by 213 · see citing works
FGF21 and the late adaptive response to starvation in humans
Fazeli, P. K., Lun, M., Kim, S. M., Bredella, M. A., Wright, S., Zhang, Y., Lee, H., Catana, C., Klibanski, A., Patwari, P., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci83349 · Cited by 214 · see citing works
Jornayvaz, F. R., Jurczak, M. J., Lee, H., Birkenfeld, A. L., Frederick, D. W., Zhang, D., Zhang, X., Samuel, V. T., & Shulman, G. I. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00361.2010 · Cited by 212 · see citing works
Circulating fibroblast growth factors as metabolic regulators--a critical appraisal.
Angelin, B., Larsson, T., & Rudling, M. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.11.001 · Cited by 210 · see citing works
Inventing new medicines: The FGF21 story
Kharitonenkov, A., & Adams, A. C. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2013.12.003 · Cited by 198 · see citing works
Li, H., Gao, Z., Zhang, J., Ye, X., Xu, A., Ye, J., & Jia, W. (2012) · Diabetes · doi:10.2337/db11-0846 · Cited by 193 · see citing works
Lack of Overt FGF21 Resistance in Two Mouse Models of Obesity and Insulin Resistance
Hale, C., Chen, M. M., Stanislaus, S., Chinookoswong, N., Hager, T., Wang, M., Véniant, M. M., & Xu, J. (2012) · Endocrinology · doi:10.1210/en.2010-1262 · Cited by 185 · see citing works
Jiang, S., Cheng, Y., Fang, Q., Shao, M., Zhang, Y., Liu, Y., Deng, Y., Shan, B., Liu, J., Li, H., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.565960 · Cited by 183 · see citing works
Yu, H., Xia, F., Lam, K. S., Wang, Y., Bao, Y., Zhang, J., Gu, Y., Zhou, P., Lu, J., Jia, W., et al. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2010.155184 · Cited by 170 · see citing works
Going Back to the Biology of FGF21: New Insights
Lewis, J. E., Ebling, F. J. P., Samms, R. J., & Tsintzas, K. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.05.007 · Cited by 164 · see citing works
Self-citationA critical role for ChREBP-mediated FGF21 secretion in hepatic fructose metabolism
Fisher, F. M., Kim, M., Doridot, L., Cunniff, J. C., Parker, T. S., Levine, D. M., Hellerstein, M. K., Hudgins, L. C., Maratos-Flier, E., & Herman, M. A. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2016.11.008 · Cited by 166 · see citing works
Ljubicic, V., Miura, P., Burt, M., Boudreault, L., Khogali, S. E. O., Lunde, J. A., Renaud, J.-M., & Jasmin, B. J. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr265 · Cited by 164 · see citing works
FGF21-based pharmacotherapy – potential utility for metabolic disorders
Gimeno, R. E., & Moller, D. E. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2014.03.001 · Cited by 163 · see citing works
Liu, J., Xu, Y., Hu, Y., & Wang, G. (2014) · Metabolism · doi:10.1016/j.metabol.2014.11.009 · Cited by 137 · see citing works
Feingold, K. R., Grünfeld, C., Heuer, J. G., Gupta, A., Cramer, M. S., Zhang, T., Shigenaga, J. K., Patzek, S. M., Chan, Z. W., Moser, A. H., et al. (2012) · Endocrinology · doi:10.1210/en.2011-1496 · Cited by 130 · see citing works
A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response
Iroz, A., Montagner, A., Benhamed, F., Levavasseur, F., Polizzi, A., Anthony, E., Régnier, M., Fouché, E., Lukowicz, C., Cauzac, M., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.065 · Cited by 128 · see citing works
Hoong, C. W. S., & Chua, M. W. J. (2021) · Endocrinology · doi:10.1210/endocr/bqab079 · Cited by 112 · see citing works
Samson, S. L., Sathyanarayana, P., Jogi, M., Gonzalez, E. V., Gutierrez, A., Krishnamurthy, R., Muthupillai, R., Chan, L., & Bajaj, M. (2011) · Diabetologia · doi:10.1007/s00125-011-2317-z · Cited by 110 · see citing works
Regulation of FGF21 Expression and Secretion by Retinoic Acid Receptor-related Orphan Receptor α
Wang, Y., Solt, L. A., & Burris, T. P. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.102160 · Cited by 106 · see citing works
PPARβ/δ: A Key Therapeutic Target in Metabolic Disorders
Palomer, X., Barroso, E., Pizarro‐Delgado, J., Peña, L., Botteri, G., Zarei, M., Aguilar-Recarte, D., Montori-Grau, M., & Vázquez‐Carrera, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030913 · Cited by 105 · see citing works
Glucose and Lipid Homeostasis and Inflammation in Humans Following an Isocaloric Ketogenic Diet
ROSENBAUM, M. S., Hall, K. D., Guo, J., Ravussin, É., Mayer, L. S., Reitman, M. L., Smith, S. R., Walsh, B. T., & Leibel, R. L. (2019) · Obesity · doi:10.1002/oby.22468 · Cited by 105 · see citing works
FGF21 and the physiological regulation of macronutrient preference
Hill, C. M., Qualls-Creekmore, E., Berthoud, H.-R., Soto, P., Yu, S., McDougal, D. H., Münzberg, H., & Morrison, C. D. (2020) · Endocrinology · doi:10.1210/endocr/bqaa019 · Cited by 99 · see citing works
Emerging role of fibroblast growth factors 15/19 and 21 as metabolic integrators in the liver
Cicione, C., Degirolamo, C., & Moschetta, A. (2012) · Hepatology · doi:10.1002/hep.25929 · Cited by 95 · see citing works
Fibroblast growth factor 21 is a metabolic regulator that plays a role in the adaptation to ketosis
Domouzoglou, E. M., & Maratos–Flier, E. (2011) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.001941 · Cited by 93 · see citing works
Singhal, G., Kumar, G., Chan, S., Fisher, F. M., Ma, Y., Vardeh, H. G., Nasser, I. A., Flier, J. S., & Maratos-Flier, E. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.03.002 · Cited by 87 · see citing works
Fibroblast Growth Factor 21 and the Adaptive Response to Nutritional Challenges
Martínez‐Garza, Ú., Torres‐Oteros, D., Yarritu, A., Marrero, P. F., Haro, D., & Relat, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194692 · Cited by 87 · see citing works
Fibroblast Growth Factor 21 As an Emerging Therapeutic Target for Type 2 Diabetes Mellitus
So, W. Y., & Leung, P. S. (2016) · Medicinal Research Reviews · doi:10.1002/med.21390 · Cited by 85 · see citing works
Murata, Y., Konishi, M., & Itoh, N. (2011) · Journal of Nutrition and Metabolism · doi:10.1155/2011/981315 · Cited by 85 · see citing works
Circulating FGF21 Levels in Human Health and Metabolic Disease
Keuper, M., Häring, H., & Staiger, H. (2019) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-0879-2968 · Cited by 82 · see citing works
Fibroblast growth factor 21 is not required for the antidiabetic actions of the thiazoladinediones
Adams, A. C., Coşkun, T., Cheng, C., O’Farrell, L. S., DuBois, S. L., & Kharitonenkov, A. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.05.005 · Cited by 75 · see citing works
Transcriptional control of physiological and pathological processes by the nuclear receptor PPARβ/δ
Tan, N. S., Vázquez‐Carrera, M., Montagner, A., Sng, M. K., Guillou, H., & Wahli, W. (2016) · Progress in Lipid Research · doi:10.1016/j.plipres.2016.09.001 · Cited by 74 · see citing works
Unraveling the Effects of PPARβ/δ on Insulin Resistance and Cardiovascular Disease
Vázquez‐Carrera, M. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.02.008 · Cited by 71 · see citing works
Spann, R. A., Morrison, C. D., & den Hartigh, L. J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.802541 · Cited by 75 · see citing works
Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology
Li, H., Zhang, J., & Jia, W. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0244-8 · Cited by 69 · see citing works
Homeostatic sensing of dietary protein restriction: a case for FGF21
Hill, C. M., Berthoud, H.-R., Münzberg, H., & Morrison, C. D. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.06.002 · Cited by 68 · see citing works
Use of FGF-21 as a Biomarker of Mitochondrial Disease in Clinical Practice
Morovat, A., Weerasinghe, G. R., Nesbitt, V., Hofer, M., Agnew, T., Quaghebeur, G., Sergeant, K., Fratter, C., Guha, N., Mirzazadeh, M., et al. (2017) · Journal of Clinical Medicine · doi:10.3390/jcm6080080 · Cited by 68 · see citing works
Factors mediating exercise‐induced organ crosstalk
Sabaratnam, R., Wojtaszewski, J. F. P., & Højlund, K. (2022) · Acta Physiologica · doi:10.1111/apha.13766 · Cited by 69 · see citing works
Kouno, T., Liu, X., Zhao, H., Kisseleva, T., Cable, E. E., & Schnabl, B. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102056 · Cited by 67 · see citing works
Metabolic role of fibroblast growth factor 21 in liver, adipose and nervous system tissues
Lin, X., Liu, Y. B., & Hu, H. (2017) · Biomedical Reports · doi:10.3892/br.2017.890 · Cited by 61 · see citing works
Effect of Nutrition on Statural Growth
Gat‐Yablonski, G., & Luca, F. D. (2017) · Hormone Research in Paediatrics · doi:10.1159/000456547 · Cited by 61 · see citing works
Tyynismaa, H., Raivio, T., Hakkarainen, A., Ortega‐Alonso, A., Lundbom, N. M. I., Kaprio, J. A., Rissanen, A., Suomalainen, A., & Pietiläinen, K. H. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1326 · Cited by 61 · see citing works
Struik, D., Dommerholt, M. B., & Jonker, J. W. (2019) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000599 · Cited by 61 · see citing works
FGF21 Is Not a Major Mediator for Bone Homeostasis or Metabolic Actions of PPARα and PPARγ Agonists
Li, X., Stanislaus, S., Asuncion, F., Niu, Q.-T., Chinookoswong, N., Villasenor, K., Wang, J., Wong, P., Boyce, R., Dwyer, D., et al. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2936 · Cited by 61 · see citing works
Insights into the Role of PPARβ/δ in NAFLD
Chen, J., Montagner, A., Tan, N. S., & Wahli, W. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19071893 · Cited by 60 · see citing works
Hepatokines—A novel group of exercise factors
Weigert, C., Hoene, M., & Plomgaard, P. (2019) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2216-y · Cited by 57 · see citing works
Lovrić, A., Granér, M., Björnson, E., Arif, M., Benfeitas, R., Nyman, K., Ståhlman, M., Pentikäinen, M. O., Lundbom, J., Hakkarainen, A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-31865-w · Cited by 61 · see citing works
Physiological modulation of circulating FGF21: relevance of free fatty acids and insulin
Mai, K., Bobbert, T., Groth, C., Aßmann, A., Meinus, S., Kraatz, J., Andres, J., Arafat, A. M., Pfeiffer, A. F. H., Möhlig, M., et al. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00020.2010 · Cited by 58 · see citing works
Relation between fibroblast growth factor–21, adiposity, metabolism, and weight reduction
Mai, K., Schwarz, F., Bobbert, T., Andres, J., Aßmann, A., Pfeiffer, A. F. H., & Spranger, J. (2010) · Metabolism · doi:10.1016/j.metabol.2010.02.016 · Cited by 58 · see citing works
Allard, C., Bonnet, F., Xu, B., Coons, L. A., Albarado, D. C., Hill, C. M., Fagherazzi, G., Korach, K. S., Levin, E. R., Lefante, J. J., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.02.002 · Cited by 58 · see citing works
Increased Placental Expression of Fibroblast Growth Factor 21 in Gestational Diabetes Mellitus
Nitert, M. D., Barrett, H. L., Kubala, M. H., Scholz‐Romero, K., Denny, K. J., Woodruff, T. M., McIntyre, D. H., & Callaway, L. K. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2581 · Cited by 57 · see citing works
Fougerat, A., Bruse, J., Polizzi, A., Montagner, A., Guillou, H., & Wahli, W. (2024) · Progress in Lipid Research · doi:10.1016/j.plipres.2024.101303 · Cited by 54 · see citing works
Domingo, P., Gallego-Escuredo, J. M., Domingo, J. C., Gutiérrez, M. D. M., Mateo, G. M., Fernández, I., Vidal, F., Giralt, M., & Villarroya, F. (2010) · AIDS · doi:10.1097/qad.0b013e3283400088 · Cited by 53 · see citing works
Hashidume, T., Kato, A., Tanaka, T., Miyoshi, S., Itoh, N., Nakata, R., Inoue, H., Oikawa, A., Nakai, Y., Shimizu, M., et al. (2016) · Scientific Reports · doi:10.1038/srep28183 · Cited by 52 · see citing works
Zarei, M., Aguilar-Recarte, D., Palomer, X., & Vázquez‐Carrera, M. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154342 · Cited by 49 · see citing works
Hepatic hormone FGF21 and its analogues in clinical trials
Shao, W., & Jin, T. (2021) · Chronic Diseases and Translational Medicine · doi:10.1016/j.cdtm.2021.08.005 · Cited by 46 · see citing works
Early investigational drugs targeting PPAR-α for the treatment of metabolic disease
Liu, Z.-M., Hu, M., Chan, P., & Tomlinson, B. (2015) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2015.1006359 · Cited by 45 · see citing works
Metabolic actions of fibroblast growth factor 21
Ramos, D. C., Aguilar-Salinas, C. A., & Gomez-Perez, F. J. (2012) · Current Opinion in Pediatrics · doi:10.1097/mop.0b013e3283557d22 · Cited by 45 · see citing works
Stemmer, K., Zani, F., Habegger, K. M., Neff, C., Kotzbeck, P., Bauer, M., Yalamanchilli, S., Azad, A., Lehti, M., Martins, P. J. F., et al. (2015) · Diabetologia · doi:10.1007/s00125-015-3668-7 · Cited by 44 · see citing works
Kim, E. R., Kim, S. R., Cho, W., Lee, S., Kim, S. H., Kim, J. H., Choi, E., Kim, J., Yu, J., Lee, B., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.843520 · Cited by 44 · see citing works
Fibroblast growth factor 21 in heart failure
Tucker, W., Tucker, B., Rye, K., & Ong, K. L. (2022) · Heart Failure Reviews · doi:10.1007/s10741-022-10268-0 · Cited by 44 · see citing works
Benetti, E., Mastrocola, R., Rogazzo, M., Chiazza, F., Aragno, M., Fantozzi, R., Collino, M., & Minetto, M. A. (2013) · Mediators of Inflammation · doi:10.1155/2013/509502 · Cited by 42 · see citing works
Heme-Regulated eIF2α Kinase Modulates Hepatic FGF21 and Is Activated by PPARβ/δ Deficiency
Zarei, M., Barroso, E., Leiva, R., Barniol‐Xicota, M., Pujol, E., Escolano, C., Vázquez, S., Palomer, X., Pardo, V., González‐Rodríguez, Á., et al. (2016) · Diabetes · doi:10.2337/db16-0155 · Cited by 42 · see citing works
Curcumin and dietary polyphenol research: beyond drug discovery
Jin, T. (2018) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.179 · Cited by 43 · see citing works
Fibroblast growth factor 21 in metabolic syndrome
Yang, M., Liu, C., Jiang, N., Liu, Y., Luo, S., Li, C., Zhao, H., Han, Y., Chen, W., Li, L., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1220426 · Cited by 39 · see citing works
The potential effect of metformin on fibroblast growth factor 21 in type 2 diabetes mellitus (T2DM)
Al-Kuraishy, H. M., Al-Gareeb, A. I., Saad, . M., & Batiha, G. E. (2023) · Inflammopharmacology · doi:10.1007/s10787-023-01255-4 · Cited by 36 · see citing works
Elevated Serum Fibroblast Growth Factor 21 in Humans with Acute Pancreatitis
Shenoy, V. K., Beaver, K. M., Fisher, F. M., Singhal, G., Dushay, J. R., Maratos–Flier, E., & Flier, S. N. (2016) · PLoS ONE · doi:10.1371/journal.pone.0164351 · Cited by 36 · see citing works
Metabolic actions of FGF21: molecular mechanisms and therapeutic implications
Ge, X., Wang, Y., Lam, K. S., & Xu, A. (2012) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2012.06.011 · Cited by 35 · see citing works
Protein Appetite at the Interface between Nutrient Sensing and Physiological Homeostasis
Khan, M. S. H., Spann, R. A., Münzberg, H., Yu, S., Albaugh, V. L., He, Y., Berthoud, H., & Morrison, C. D. (2021) · Nutrients · doi:10.3390/nu13114103 · Cited by 35 · see citing works
Nutritional Ketosis as a Potential Treatment for Alcohol Use Disorder
Mahajan, V. R., Elvig, S. K., Vendruscolo, L. F., Koob, G. F., Darcey, V. L., King, M. T., Kranzler, H. R., Volkow, N. D., & Wiers, C. E. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.781668 · Cited by 34 · see citing works
Wu, C., Gilroy, R. K., Taylor, R. M., Olyaee, M. S., Abdulkarim, B., Forster, J., O’Neil, M. F., Damjanov, I., & Wan, Y. Y. (2010) · Hepatology · doi:10.1002/hep.24645 · Cited by 33 · see citing works
Huang, T., Linden, M. A., Fuller, S. E., Goldsmith, F., Simon, J., Batdorf, H. M., Scott, M. C., Essajee, N. M., Brown, J. M., & Noland, R. C. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00410.2020 · Cited by 32 · see citing works
Higher serum levels of fibroblast growth factor 21 in old patients with cachexia
Franz, K., Ost, M., Otten, L., Herpich, C., Coleman, V., Endres, A., Klaus, S., Müller‐Werdan, U., & Norman, K. (2018) · Nutrition · doi:10.1016/j.nut.2018.11.004 · Cited by 31 · see citing works
Whytock, K. L., Carnero, E. A., Vega, R. B., Tillner, J., Bock, C., Chivukula, K., Yi, F., Meyer, C., Smith, S. R., & Sparks, L. M. (2021) · Obesity · doi:10.1002/oby.23141 · Cited by 30 · see citing works
FGF21 signalling pathway and metabolic traits – genetic association analysis
Kaess, B. M., Barnes, T. A., Stark, K. J., Charchar, F. J., Waterworth, D. M., Song, K. S., Wang, W. Y. S., Vollenweider, P., Waeber, G., Mooser, V., et al. (2010) · European Journal of Human Genetics · doi:10.1038/ejhg.2010.130 · Cited by 30 · see citing works
Liao, Y., Wang, Y.-H., Wu, C.-Y., Hsu, F.-Y., Chien, C.-Y., & Lee, Y.-C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062934 · Cited by 29 · see citing works
Murphy, M., Samms, R. J., Warner, A., Bolborea, M., Barrett, P., Fowler, M. J., Brameld, J. M., Tsintzas, K., Kharitonenkov, A., Adams, A. C., et al. (2012) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2012.02383.x · Cited by 29 · see citing works
Self-citationFibroblast Growth Factor 21: A Novel Metabolic Regulator
Seo, J. A., & Kim, N. H. (2012) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2012.36.1.26 · Cited by 27 · see citing works
Fibroblast Growth Factor 21 Facilitates the Homeostatic Control of Feeding Behavior
Wu, C.-T., CHAFFIN, A. T. B., & Ryan, K. K. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11030580 · Cited by 22 · see citing works
Pérez‐Martí, A., Sandoval, V., Marrero, P. F., Haro, D., & Relat, J. (2016) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2016-0034 · Cited by 24 · see citing works
Estrogen-Wnt signaling cascade regulates expression of hepatic fibroblast growth factor 21
Badakhshi, Y., Shao, W., Liu, D., Tian, L., Pang, J., Gu, J., Hu, J., & Jin, T. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00638.2020 · Cited by 23 · see citing works
Plasma mannose-binding lectin is stimulated by PPARα in humans
Rakhshandehroo, M., Stienstra, R., de Wit, N. J. W., Bragt, M. C. E., Haluzı́k, M., Mensink, R. P., Müller, M. M., & Kersten, S. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00299.2011 · Cited by 23 · see citing works
Liu, X., Zhang, Y., Ma, C., Lin, J., & Du, J. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-07142-5 · Cited by 22 · see citing works
McCullough, D., Harrison, T., Boddy, L. M., Enright, K. J., Amirabdollahian, F., Schmidt, M., Doenges, K., Quinn, K. D., Reisdorph, N. A., Mazidi, M., et al. (2022) · Nutrients · doi:10.3390/nu14183691 · Cited by 22 · see citing works
Chen, H., Dardik, B. N., Qiu, L., Ren, X., Caplan, S. L., Burkey, B. F., Boettcher, B. R., & Gromada, J. (2010) · Endocrinology · doi:10.1210/en.2009-1366 · Cited by 22 · see citing works
- Authors
- Christodoulides, C., Dyson, P., Sprecher, D., Tsintzas, K., & Karpe, F.
- Affiliations
- Churchill Hospital (GB)
- GlaxoSmithKline (United States) (US)
- University of Nottingham (GB)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-09-01
- Volume
- 94
- Issue
- 9
- Pages
- 3594-3601
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2140313261
- Cited by
- 153
- References
- 45
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 11 · 2021: 11 · 2020: 8 · 2019: 12 · 2018: 11 · 2017: 9 · 2016: 12 · 2015: 6 · 2014: 9 · 2013: 4 · 2012: 13
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- Wellcome Trust
- 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 › Dietary Effects on Health
- Keywords
- FGF21, PPARα agonist, PPARδ agonist, PPARγ agonists, ketosis, ketogenic diet, fasting and refeeding, beta-hydroxybutyrate, GW501516, rosiglitazone, obesity, metabolic regulation
- MeSH terms
- Adult, Fibroblast Growth Factors, Humans, Ketosis, Male, Prospective Studies, Peroxisome Proliferator-Activated Receptors, Diet, Ketogenic
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
