FGF21 is not required for glucose homeostasis, ketosis or tumour suppression associated with ketogenic diets in mice
Open accessAbstract
Aims/hypothesis Ketogenic diets (KDs) have increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. The metabolic benefits of KDs are regularly ascribed to enhanced hepatic secretion of fibroblast growth factor 21 (FGF21) and its systemic effects on fatty-acid oxidation, energy expenditure (EE) and body weight. Ambiguous data from Fgf21-knockout animal strains and low FGF21 concentrations reported in humans with ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating the therapeutic benefits of KDs on metabolism and cancer.Methods We established a dietary model of increased vs decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted of protein or enriched with protein. We furthermore used wild-type and Fgf21-knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumour growth after transplantation of Lewis lung carcinoma cells.Results Hepatic and circulating, but not adipose tissue, FGF21 levels were profoundly increased by protein starvation, independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycaemia upon protein and carbohydrate starvation and is therefore not needed for the effects of KDs on EE. Furthermore, the tumour-suppressing effects of KDs were independent of FGF21 and, rather, driven by concomitant protein and carbohydrate starvation.Conclusions/interpretation Our data indicate that the multiple systemic effects of KD exposure in mice, previously ascribed to increased FGF21 secretion, are rather a consequence of protein malnutrition.
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
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?
Other groups have reported that FGF21 is not required for regulating glucose homeostasis and ketosis induced by ketogenic diets.
“However, these conclusions have been controversial because other groups have reported that FGF21 is not required for regulating glucose homeostasis and ketosis induced by ketogenic diets (97, 123).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [123]
The effect of high carbohydrate and low protein to increase FGF21 appears to be regulated independently.
“the effect of high carbohydrate and low protein to increase FGF21 appears to be regulated independently”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [163]
The increase in FGF21 is directly related to reduced protein intake, as it occurs in settings of both low and high carbohydrate and low and high fat.
“This increase in FGF21 is directly related to reduced protein intake, as it occurs in settings of both low and high carbohydrate and low and high fat”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [163]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610 · see citing works
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
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
Yoon, J. C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C. R., Granner, D. K., et al. (2001) · Nature · doi:10.1038/35093050 · Cited by 1,821 · see citing works
A Randomized Trial of a Low-Carbohydrate Diet for Obesity
Foster, G. D., Wyatt, H. R., Hill, J. O., McGuckin, B. G., Brill, C., Mohammed, B. S., Szapary, P. O., Rader, D. J., Edman, J. S., & Klein, S. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022207 · Cited by 1,794 · see citing works
Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression
Lecker, S. H., Jagoe, R. T., Gilbert, A., Gomes, M., Baracos, V., Bailey, J., Price, S. R., Mitch, W. E., & Goldberg, A. L. (2004) · The FASEB Journal · doi:10.1096/fj.03-0610com · Cited by 1,539 · 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
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
Brehm, B. J., Seeley, R. J., Daniels, S. R., & D’Alessio, D. A. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021480 · Cited by 830 · see citing works
Self-citationPotthoff, M. J., Inagaki, T., Satapati, S., Ding, X., He, T., Goetz, R., Mohammadi, M., Finck, B. N., Mangelsdorf, D. J., Kliewer, S. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904187106 · Cited by 704 · 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 · cited 2× · see citing works
“This stands in contrast to previous findings by Leager et al [39] showing increased EE in mice fed a protein-restricted regular diet.”
ResultDutchak, 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
FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss
Owen, B. M., Ding, X., Morgan, D. A., Coate, K. C., Bookout, A. L., Rahmouni, K., Kliewer, S. A., & Mangelsdorf, D. J. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.07.012 · Cited by 523 · 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
A high-fat, ketogenic diet induces a unique metabolic state in mice
Kennedy, A. R., Pissios, P., Otu, H., Xue, B., Asakura, K., Furukawa, N., Marino, F. E., Liu, F.-F., Kahn, B. B., Libermann, T. A., et al. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00717.2006 · Cited by 420 · see citing works
Fibroblast Growth Factor 21-Deficient Mice Demonstrate Impaired Adaptation to Ketosis
Badman, M. K., Koester, A., Flier, J. S., Kharitonenkov, A., & Maratos-Flier, E. (2009) · Endocrinology · doi:10.1210/en.2009-0532 · Cited by 362 · see citing works
Hotta, Y., Nakamura, H., Konishi, M., Murata, Y., Takagi, H., Matsumura, S., Inoue, K., Fushiki, T., & Itoh, N. (2009) · Endocrinology · doi:10.1210/en.2009-0119 · Cited by 352 · see citing works
Nebeling, L. C., Miraldi, F. D., Shurin, S. B., & Lerner, E. (1995) · Journal of the American College of Nutrition · doi:10.1080/07315724.1995.10718495 · Cited by 312 · see citing works
Sarruf, D. A., Thaler, J. P., Morton, G. J., German, J. P., Fischer, J. D., Ogimoto, K., & Schwartz, M. W. (2010) · Diabetes · doi:10.2337/db09-1878 · Cited by 287 · see citing works
Role of glucose and ketone bodies in the metabolic control of experimental brain cancer
Seyfried, T. N., Sanderson, T., El‐Abbadi, M. M., McGowan, R., & Mukherjee, P. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6601269 · Cited by 267 · see citing works
Activating transcription factor 4-dependent induction of FGF21 during amino acid deprivation
De Sousa-Coelho, A. L., Marrero, P. F., & Haro, D. (2012) · Biochemical Journal · doi:10.1042/bj20111748 · Cited by 246 · see citing works
Integrated Regulation of Hepatic Metabolism by Fibroblast Growth Factor 21 (FGF21) in Vivo
Fisher, F. M., Estall, J. L., Adams, A. C., Antonellis, P. J., Bina, H. A., Flier, J. S., Kharitonenkov, A., Spiegelman, B. M., & Maratos–Flier, E. (2011) · Endocrinology · doi:10.1210/en.2011-0281 · Cited by 229 · see citing works
Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases
Paoli, A., Bianco, A., Damiani, E., & Bosco, G. (2014) · BioMed Research International · doi:10.1155/2014/474296 · Cited by 221 · 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
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
Beneficial effects of ketogenic diet in obese diabetic subjects
Dashti, H. M., Mathew, T. C., Khadada, M., Al-Mousawi, M., Talib, H., Asfar, S., Behbahani, A. I., & Al-Zaid, N. S. (2007) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-007-9448-z · Cited by 172 · see citing works
LY2405319, an engineered FGF21 variant, improves the metabolic status of diabetic monkeys
Adams, A. C., Halstead, C. A., Hansen, B. C., Irizarry, A. R., Martin, J. A., Myers, S. R., Reynolds, V. L., Smith, H. W., Wroblewski, V. J., & Kharitonenkov, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065763 · Cited by 169 · see citing works
Rational Design of a Fibroblast Growth Factor 21-Based Clinical Candidate, LY2405319
Kharitonenkov, A., Beals, J. M., Micanovic, R., Strifler, B. A., Rathnachalam, R., Wroblewski, V. J., Li, S., Köester, A., Ford, A. M., Coşkun, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058575 · Cited by 168 · 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
Müller, T. D., Sullivan, L. M., Habegger, K., Yi, C., Kabra, D., Grant, E., Ottaway, N., Krishna, R., Holland, J., Hembree, J., et al. (2012) · Journal of Peptide Science · doi:10.1002/psc.2408 · Cited by 156 · see citing works
Self-citationChristodoulides, C., Dyson, P., Sprecher, D., Tsintzas, K., & Karpe, F. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0111 · Cited by 153 · see citing works
Metabolic management of brain cancer
Seyfried, T. N., Kiebish, M. A., Marsh, J., Shelton, L. M., Huysentruyt, L. C., & Mukherjee, P. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.08.009 · Cited by 146 · see citing works
Stark, R., Pasquel, F., Turcu, A., Pongratz, R. L., Roden, M., Cline, G., Shulman, G., & Kibbey, R. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.011775 · Cited by 146 · see citing works
Bielohuby, M., Menhofer, D., Kirchner, H., Stoehr, B. J. M., Müller, T. D., Stock, P., Hempel, M., Stemmer, K., Pfluger, P. T., Kienzle, E., et al. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00478.2010 · Cited by 88 · see citing works
Self-citationStemmer, K., Kotzbeck, P., Zani, F., Bauer, M., Neff, C. E., Müller, T. D., Pfluger, P. T., Seeley, R. J., & Divanovic, S. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.187 · Cited by 79 · see citing works
Self-citationFibroblast 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
Stemmer, K., Bielohuby, M., Grayson, B. E., Begg, D. P., Chambers, A. P., Neff, C., Woods, S. C., Erben, R. G., Tschöp, M. H., Bidlingmaier, M., et al. (2013) · Endocrinology · doi:10.1210/en.2012-2130 · Cited by 66 · see citing works
Self-citationMethionine and choline regulate the metabolic phenotype of a ketogenic diet
Pissios, P., Hong, S., Kennedy, A. R., Prasad, D., Liu, F., & Maratos–Flier, E. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.07.003 · Cited by 61 · see citing works
Dietary therapies for epilepsy: Future research
Kessler, S. K., Neal, E. G., Camfield, C., & Kossoff, E. H. (2011) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2011.02.018 · Cited by 55 · see citing works
Fgf21 Impairs Adipocyte Insulin Sensitivity in Mice Fed a Low-Carbohydrate, High-Fat Ketogenic Diet
Murata, Y., Nishio, K., Mochiyama, T., Konishi, M., Shimada, M., Ohta, H., & Itoh, N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069330 · Cited by 54 · see citing works
Carbohydrate for weight and metabolic control: Where do we stand?
Acheson, K. J. (2010) · Nutrition · doi:10.1016/j.nut.2009.07.002 · Cited by 42 · see citing works
Wiese, T. J., Lambeth, D. O., & Ray, P. D. (1991) · Comparative Biochemistry and Physiology Part B Comparative Biochemistry · doi:10.1016/0305-0491(91)90378-q · Cited by 41 · see citing works
Batty, R. S., Blaxter, J. H. S., & Bone, Q. (1991) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(91)90473-p · Cited by 26 · see citing works
FGF21 suppresses hepatic glucose production through the activation of atypical protein kinase Cι/λ
Kong, L.-J., Feng, W., Wright, M., Chen, Y., Dallas-Yang, Q., Zhou, Y., & Berger, J. P. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.11.065 · Cited by 25 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Fasting and cancer: molecular mechanisms and clinical application
Nencioni, A., Caffa, I., Cortellino, S., & Longo, V. D. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0061-0 · Cited by 518 · see citing works
Ketogenic diet in the treatment of cancer – Where do we stand?
Weber, D. D., Aminzadeh-Gohari, S., Tulipan, J., Catalano, L., Feichtinger, R. G., & Kofler, B. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.06.026 · Cited by 464 · see citing works
Regulation of Ketone Body Metabolism and the Role of PPARα
Grabacka, M., Pierzchalska, M., Dean, M., & Reiss, K. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122093 · Cited by 305 · 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
Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework
Solon-Biet, S. M., Cogger, V. C., Pulpitel, T., Heblinski, M., Wahl, D., McMahon, A. C., Warren, A., Durrant-Whyte, J., Walters, K. A., Krycer, J. R., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.001 · Cited by 212 · see citing works
Klement, R. J. (2017) · Medical Oncology · doi:10.1007/s12032-017-0991-5 · Cited by 140 · see citing works
Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities
Talib, W. H., Mahmod, A. I., Kamal, A., Rashid, H. M., Alashqar, A. M. D., Khater, S. H., Jamal, D., & Waly, M. I. (2021) · Current Issues in Molecular Biology · doi:10.3390/cimb43020042 · Cited by 124 · see citing works
Klement, R. J., & Fink, M. K. (2016) · Oncogenesis · doi:10.1038/oncsis.2016.2 · Cited by 115 · see citing works
Nakamura, K., Tonouchi, H., Sasayama, A., & Ashida, K. (2018) · Nutrients · doi:10.3390/nu10020206 · Cited by 105 · see citing works
Kulaj, K., Harger, A., Bauer, M., Çalışkan, Ö. Ş., Gupta, T. K., Chiang, D. M., Milbank, E., Reber, J., Karlas, A., Kotzbeck, P., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36148-1 · Cited by 110 · see citing works
Self-citationFibroblast growth factor 21 night watch: advances and uncertainties in the field
Kharitonenkov, A., & DiMarchi, R. D. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12580 · Cited by 97 · 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
Zhang, N., Liu, C., Jin, L., Zhang, R., Wang, T., Wang, Q., Chen, J., Yang, F., Siebert, H., & Zheng, X. (2020) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.0c04041 · Cited by 87 · 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
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
Fibroblast growth factor-21 controls dietary protein intake in male mice
Larson, K. R., Chaffin, A. T.-B., Goodson, M. L., Fang, Y., & Ryan, K. K. (2019) · Endocrinology · doi:10.1210/en.2018-01056 · Cited by 68 · see citing works
Protein restriction and cancer
Yin, J., Ren, W., Huang, X., Li, T., & Yin, Y. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.03.004 · Cited by 64 · see citing works
Long, F., Bhatti, M. R., Kellenberger, A., Sun, W., Modica, S., Höring, M., Liebisch, G., Krieger, J.-P., Wolfrum, C., & Challa, T. D. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101675 · Cited by 62 · see citing works
Amino acid transporters in the regulation of insulin secretion and signalling
Javed, K., & Fairweather, S. J. (2019) · Biochemical Society Transactions · doi:10.1042/bst20180250 · Cited by 59 · see citing works
The impact of keto-adaptation on exercise performance and the role of metabolic-regulating cytokines
Sherrier, M. C., & Li, H. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz145 · Cited by 56 · see citing works
Cancer Treatment With the Ketogenic Diet: A Systematic Review and Meta-analysis of Animal Studies
Li, J., Zhang, H., & Dai, Z. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.594408 · Cited by 45 · see citing works
Ryan, K. K., Packard, A. E. B., Larson, K. R., Stout, J., Fourman, S. M., Thompson, A. M. K., Ludwick, K., Habegger, K. M., Stemmer, K., Itoh, N., et al. (2017) · Endocrinology · doi:10.1210/en.2017-00486 · Cited by 40 · see citing works
Self-citationQian, J., Tikk, K., Weigl, K., Balavarca, Y., & Brenner, H. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0280-x · 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
Hepatic FGF21: Its Emerging Role in Inter-Organ Crosstalk and Cancers
Sui, Y., & Chen, J. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.76924 · Cited by 33 · see citing works
Smolensky, I. V., Zajac-Bakri, K., Odermatt, T. S., Brégère, C., Cryan, J. F., Guzman, R. G., Timper, K., & Inta, D. (2023) · Scientific Reports · doi:10.1038/s41598-023-43587-9 · Cited by 33 · see citing works
Caloric Restriction Prevents Carcinogen-Initiated Liver Tumorigenesis in Mice
Ploeger, J. M., Manivel, J. C., Boatner, L. N., & Mashek, D. G. (2017) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-17-0174 · Cited by 25 · 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
Liao, S., Li, P., Wang, J., Zhang, Q., Xu, D., Yang, M., & Kong, L. (2016) · Toxicology Research · doi:10.1039/c6tx00082g · Cited by 24 · see citing works
Li, Y., Huang, J., Jiang, Z., Jiao, Y., & Wang, H. (2017) · PubMed Central · Cited by 22 · see citing works
Kalafut, K. C., Mitchell, S. J., MacArthur, M. R., & Mitchell, J. R. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.839341 · Cited by 21 · see citing works
Shirian, F. I., Karimi, M., Alipour, M., Salami, S., Nourbakhsh, M., Nekufar, S., Safari‐Alighiarloo, N., & Tavakoli‐Yaraki, M. (2024) · Molecular Biology Reports · doi:10.1007/s11033-024-09501-w · Cited by 20 · see citing works
Weber, A. J., Medak, K. D., Townsend, L. K., & Wright, D. C. (2022) · The Journal of Physiology · doi:10.1113/jp283469 · Cited by 17 · see citing works
Fibroblast Growth Factor 21-Null Mice Do Not Exhibit an Impaired Response to Fasting
Antonellis, P. J., Hayes, M. P., & Adams, A. C. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00077 · Cited by 17 · see citing works
FGF21 mediating the Sex-dependent Response to Dietary Macronutrients
Sauza, K. A. S., & Ryan, K. K. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae363 · Cited by 14 · see citing works
Catalano, L., Aminzadeh-Gohari, S., Weber, D. D., Poupardin, R., Stefan, V. E., Smiles, W. J., Tevini, J., Feichtinger, R. G., Derdak, S. V., Bilban, M., et al. (2023) · Metabolites · doi:10.3390/metabo13080910 · Cited by 7 · see citing works
Huang, Y., Zhu, Y., Shi, J., Liu, R., Zeng, T., & Han, L. (2023) · PubMed Central · doi:10.12122/j.issn.1673-4254.2023.10.12 · Cited by 4 · see citing works
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 · see citing works
Al-Jada, D. N., Takruri, H. R., & Talib, W. H. (2023) · PharmaNutrition · doi:10.1016/j.phanu.2023.100340 · Cited by 2 · see citing works
Wali, J. A., Ramos-Nieves, J. M., Binia, A., & van der Beek, E. M. (2026) · Advances in Nutrition · doi:10.1016/j.advnut.2026.100713 · Cited by 1 · see citing works
Ozsoz, C. F., Yıldız, E., & Gürbüz, O. (2022) · Izmir Democracy University Health Sciences Journal · doi:10.52538/iduhes.1093564 · Cited by 1 · see citing works
The Metabolic Effects of FGF21: From Physiology to Pharmacology
Song, P. (2020) · JoLS Journal of Life Sciences · doi:10.5352/jls.2020.30.7.640 · Cited by 1 · see citing works
Insulin-sensitizing effects of fibroblast growth factor-21 in underfed sheep
dos Santos, A. C. R., McGuckin, M. M., Giesy, S. L., & Boisclair, Y. R. (2025) · Journal of Animal Science · doi:10.1093/jas/skaf217
Macronutrient Composition and Genetic Background Determine the Response to a Ketogenic DietPreprint
Zhang, Z., Moura‐Assis, A., Liu, S., Millet, A., Shaked, J., Rajan, D., Alwaseem, H., Viscio, M. I.-D., Molina, H., Birsoy, K., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.23.720368
- Authors
- Stemmer, K., Zani, F., Habegger, K. M., Neff, C., Kotzbeck, P., Bauer, M., Yalamanchilli, S., Azad, A., Lehti, M., Martins, P. J. F., Müller, T. D., Pfluger, P. T., & Seeley, R. J.
- Affiliations
- Helmholtz Munich (DE)
- University of Alabama at Birmingham (US)
- University of Cincinnati (US)
- LIKES – Foundation for Sport and Health Sciences (FI)
- University of Michigan (US)
- Corresponding author
- Seeley, Randy J.
- ORCID
- Venue
- Diabetologia
- Published
- 2015-06-23
- Volume
- 58
- Issue
- 10
- Pages
- 2414-2423
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC5144740
- OpenAlex
- W2167130564
- Cited by
- 44
- References
- 47
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 6
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- OPUS (Augsburg University) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- National Cancer Institute (U01CA141464)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK098319, T35DK060444)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Keywords
- FGF21, ketogenic diet, glucose homeostasis, ketosis, tumor suppression, protein starvation, protein malnutrition, energy expenditure, FGF21 knockout mice, Lewis lung carcinoma, dietary protein
- MeSH terms
- Adipose Tissue, Animals, Fibroblast Growth Factors, Glucose, Homeostasis, Ketosis, Liver, Neoplasms, Protein Deficiency, Mice, Knockout, Mice, 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
