Glucagon receptor signaling regulates weight loss via central KLB receptor complexes
Open accessAbstract
Glucagon regulates glucose and lipid metabolism and promotes weight loss. Thus, therapeutics stimulating glucagon receptor (GCGR) signaling are promising for obesity treatment; however, the underlying mechanism(s) have yet to be fully elucidated. We previously identified that hepatic GCGR signaling increases circulating fibroblast growth factor 21 (FGF21), a potent regulator of energy balance. We reported that mice deficient for liver Fgf21 are partially resistant to GCGR-mediated weight loss, implicating FGF21 as a regulator of glucagon’s weight loss effects. FGF21 signaling requires an obligate coreceptor (β-Klotho, KLB), with expression limited to adipose tissue, liver, pancreas, and brain. We hypothesized that the GCGR-FGF21 system mediates weight loss through a central mechanism. Mice deficient for neuronal Klb exhibited a partial reduction in body weight with chronic GCGR agonism (via IUB288) compared with controls, supporting a role for central FGF21 signaling in GCGR-mediated weight loss. Substantiating these results, mice with central KLB inhibition via a pharmacological KLB antagonist, 1153, also displayed partial weight loss. Central KLB, however, is dispensable for GCGR-mediated improvements in plasma cholesterol and liver triglycerides. Together, these data suggest GCGR agonism mediates part of its weight loss properties through central KLB and has implications for future treatments of obesity and metabolic syndrome.
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?
Previous studies in preclinical models demonstrate the potential for GcgR agonism to induce weight loss either alone or in combination with GLP-1R and/or GIPR agonism.
“Previous studies in preclinical models demonstrate the potential for GcgR agonism to induce weight loss either alone [54,55] or in combination with GLP-1R and/or GIPR agonism [43].”
From Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice (2022) · cites this paper as [55]
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 RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751 · cited 1× · see citing works
“Fecal fat content was measured following isolation of fecal lipid as previously described (71).”
Global burden of obesity in 2005 and projections to 2030
Kelly, T., Yang, W., Chen, C.-S., Reynolds, K., & He, J. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.102 · Cited by 3,319 · 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
The Fibroblast Growth Factor signaling pathway
Ornitz, D. M., & Itoh, N. (2015) · WIREs Developmental Biology · doi:10.1002/wdev.176 · Cited by 2,050 · cited 1× · see citing works
“an FGF-receptor (FGFR-1c and -3c)/Klotho (Klb) complex (28-31) that is selectively”
FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis
Fisher, F. M., Kleiner, S., Douris, N., Fox, E. C., Mepani, R. J., Verdeguer, F., Wu, J., Kharitonenkov, A., Flier, J. S., Maratos-Flier, E., et al. (2012) · Genes & Development · doi:10.1101/gad.177857.111 · Cited by 1,478 · see citing works
Self-citationXu, 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
Self-citationLong-term Drug Treatment for Obesity: A Systematic and Clinical Review
Yanovski, S. Z., & Yanovski, J. A. (2014) · JAMA · doi:10.1001/jama.2013.281361 · Cited by 876 · see citing works
Weight Loss and Improvement in Comorbidity: Differences at 5%, 10%, 15%, and Over
Ryan, D. H., & Yockey, S. R. (2017) · Current Obesity Reports · doi:10.1007/s13679-017-0262-y · Cited by 831 · see citing works
Potthoff, 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
Fon Tacer, K., Bookout, A. L., Ding, X., Kurosu, H., John, G. B., Wang, L., Goetz, R., Mohammadi, M., Kuro-o, M., Mangelsdorf, D. J., et al. (2010) · Molecular Endocrinology · doi:10.1210/me.2010-0142 · Cited by 700 · see citing works
A new glucagon and GLP-1 co-agonist eliminates obesity in rodents
Day, J. W., Ottaway, N., Patterson, J. T., Gelfanov, V., Smiley, D., Gidda, J., Findeisen, H., Bruemmer, D., Drucker, D. J., Chaudhary, N., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.209 · Cited by 641 · see citing works
Self-citationβKlotho 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
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
Circulating FGF21 Is Liver Derived and Enhances Glucose Uptake During Refeeding and Overfeeding
Markan, K. R., Naber, M. C., Ameka, M. K., Anderegg, M. D., Mangelsdorf, D. J., Kliewer, S. A., Mohammadi, M., & Potthoff, M. J. (2014) · Diabetes · doi:10.2337/db14-0595 · Cited by 590 · see citing works
Fu, L., John, L. M., Adams, S. H., Yu, X. X., Tomlinson, E., Renz, M. E., Williams, P. M., Soriano, R. H., Corpuz, R. T., Moffat, B., et al. (2004) · Endocrinology · doi:10.1210/en.2003-1671 · Cited by 580 · see citing works
FGF21 regulates metabolism and circadian behavior by acting on the nervous system
Bookout, A. L., de Groot, M. H. M., Owen, B. M., Lee, S., Gautron, L., Lawrence, H. L., Ding, X., Elmquist, J. K., Takahashi, J. S., Mangelsdorf, D. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3249 · Cited by 545 · 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
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
Self-citationGlucagon-Like Peptide 1/Glucagon Receptor Dual Agonism Reverses Obesity in Mice
Pocai, A., Carrington, P. E., Adams, J. R., Wright, M., Eiermann, G., Zhu, L., Du, X., Petrov, A., Lassman, M. E., Jiang, G., et al. (2009) · Diabetes · doi:10.2337/db09-0278 · Cited by 409 · see citing works
Obesity and its comorbid conditions
Khaodhiar, L., McCowen, K. C., & Blackburn, G. L. (1999) · Clinical cornerstone · doi:10.1016/s1098-3597(99)90002-9 · Cited by 403 · see citing works
βKlotho Is Required for Fibroblast Growth Factor 21 Effects on Growth and Metabolism
Ding, X., Boney-Montoya, J., Owen, B. M., Bookout, A. L., Coate, K. C., Mangelsdorf, D. J., & Kliewer, S. A. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.002 · Cited by 403 · 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
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
Xu, J., Stanislaus, S., Chinookoswong, N., Lau, Y. Y., Hager, T., Patel, J., Ge, H., Weiszmann, J., Lu, S.-C., Graham, M., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00348.2009 · Cited by 340 · see citing works
Obesity and Disease Management: Effects of Weight Loss on Comorbid Conditions
Anderson, J. W., & Konz, E. C. (2001) · Obesity Research · doi:10.1038/oby.2001.138 · Cited by 330 · see citing works
FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms
BonDurant, L. D., Ameka, M., Naber, M. C., Markan, K. R., Idiga, S. O., Acevedo, M. R., Walsh, S. A., Ornitz, D. M., & Potthoff, M. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.005 · Cited by 330 · 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
Self-citationFGF21 gene therapy as treatment for obesity and insulin resistance
Jiménez, V., Jambrina, C., Casana, E., Sacristan, V., MUÑOZ, S. A., Darriba, S., Rodó, J., Mallol, C., García, M., León, X., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708791 · Cited by 319 · 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
Liver-specific Activities of FGF19 Require Klotho beta
Lin, B. C., Wang, M., Blackmore, C. A., & Desnoyers, L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704244200 · Cited by 284 · see citing works
The breadth of FGF21's metabolic actions are governed by FGFR1 in adipose tissue
Adams, A. C., Yang, C., Coskun, T., Cheng, C. C., Gimeno, R. E., Luo, Y., & Kharitonenkov, A. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2012.08.007 · Cited by 266 · see citing works
Self-citationFibroblast Growth Factor 21 Mediates Specific Glucagon Actions
Habegger, K. M., Stemmer, K., Cheng, C., Müller, T. D., Heppner, K. M., Ottaway, N., Holland, J., Hembree, J. L., Smiley, D., Gelfanov, V., et al. (2013) · Diabetes · doi:10.2337/db12-1116 · Cited by 245 · see citing works
Self-citationCellular Mechanisms by Which FGF21 Improves Insulin Sensitivity in Male Mice
Camporez, J. P., Jornayvaz, F. R., Petersen, M. C., Pesta, D. H., Guigni, B. A., Serr, J., Zhang, D., Kahn, M., Samuel, V. T., Jurczak, M. J., et al. (2013) · Endocrinology · doi:10.1210/en.2013-1191 · Cited by 226 · 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
Self-citationGlucagon Receptor Signaling and Lipid Metabolism
Galsgaard, K. D., Pedersen, J., Knop, F. K., Holst, J. J., & Wewer Albrechtsen, N. J. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00413 · Cited by 218 · see citing works
Geng, L., Liao, B., Jin, L., Huang, Z. P., Triggle, C. R., Ding, H., Zhang, J., Huang, Y., Lin, Z., & Xu, A. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.014 · Cited by 201 · see citing works
Ryan, K. K., Kohli, R., Gutierrez-Aguilar, R., Gaitonde, S. G., Woods, S. C., & Seeley, R. J. (2013) · Endocrinology · doi:10.1210/en.2012-1891 · Cited by 185 · see citing works
FGF21 Requires βklotho to Act In Vivo
Adams, A. C., Cheng, C. C., Coskun, T., & Kharitonenkov, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049977 · Cited by 181 · see citing works
Self-citationDifferential Specificity of Endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in Complex with KLB
Yang, C., Jin, C., Li, X., Wang, F., McKeehan, W. L., & Luo, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033870 · Cited by 173 · 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
Glucagon lowers glycemia when β cells are active
Capozzi, M. E., Wait, J. B., Koech, J., Gordon, A. N., Coch, R. W., Svendsen, B., Finan, B., D’Alessio, D. A., & Campbell, J. E. (2019) · JCI Insight · doi:10.1172/jci.insight.129954 · Cited by 168 · see citing works
Self-citationJensen-Cody, S. O., Flippo, K. H., Claflin, K. E., Yavuz, Y., Sapouckey, S. A., Walters, G. C., Usachev, Y. M., Atasoy, D., Gillum, M. P., & Potthoff, M. J. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.06.008 · Cited by 166 · see citing works
Impact of weight loss on Health-Related Quality of Life
Fontaine, K. R., Barofsky, I., Andersen, R. E., Bartlett, S. J., Wiersema, L., Cheskin, L. J., & Franckowiak, S. C. (1999) · Quality of Life Research · doi:10.1023/a:1008835602894 · Cited by 162 · see citing works
Blissmer, B. J., Riebe, D. A., Dye, G., Ruggiero, L., Greene, G. W., & Caldwell, M. J. (2006) · Health and Quality of Life Outcomes · doi:10.1186/1477-7525-4-43 · Cited by 160 · see citing works
Discrete Aspects of FGF21 In Vivo Pharmacology Do Not Require UCP1
Samms, R. J., Smith, D. P., Cheng, C. C., Antonellis, P. P., Perfield, J. W., Kharitonenkov, A., Gimeno, R. E., & Adams, A. C. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.046 · Cited by 154 · see citing works
Self-citationWanders, D., Forney, L. A., Stone, K. P., Burk, D. H., Pierse, A., & Gettys, T. W. (2017) · Diabetes · doi:10.2337/db16-1212 · Cited by 137 · see citing works
Assini, J. M., Mulvihill, E. E., Burke, A. C., Sutherland, B. G., Telford, D. E., Chhoker, S. S., Sawyez, C. G., Drangova, M., Adams, A. C., Kharitonenkov, A., et al. (2015) · Endocrinology · doi:10.1210/en.2014-2003 · Cited by 119 · see citing works
Self-citationLipid Extraction from Mouse Feces
Kraus, D., Yang, Q., & Kahn, B. B. (2015) · BIO-PROTOCOL · doi:10.21769/bioprotoc.1375 · Cited by 109 · see citing works
Fundamentals of FGF19 & FGF21 Action In Vitro and In Vivo
Adams, A. C., Coskun, T., Irizarry Rovira, A. R., Schneider, M. A., Raches, D. W., Micanovic, R., Bina, H. A., Dunbar, J. D., & Kharitonenkov, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038438 · Cited by 109 · see citing works
Self-citationCNS Leptin Action Modulates Immune Response and Survival in Sepsis
Tschöp, J., Nogueiras, R., Lockie, S. H., Kasten, K. R., Castañeda, T. R., Huber, N., Guanciale, K., Pérez–Tilve, D., Habegger, K. M., Ottaway, N., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4875-09.2010 · Cited by 98 · 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
Self-citationKim, T., Nason, S., Holleman, C., Pepin, M., Wilson, L., Berryhill, T. F., Wende, A. R., Steele, C., Young, M. E., Barnes, S., et al. (2018) · Diabetes · doi:10.2337/db17-1502 · Cited by 97 · see citing works
Self-citationGlucagon Control on Food Intake and Energy Balance
Al–Massadi, O., Fernø, J., Diéguez, C., Nogueiras, R., & Quiñones, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20163905 · Cited by 89 · 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
Cyphert, H. A., Alonge, K. M., Ippagunta, S. M., & Hillgartner, F. B. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094996 · Cited by 80 · see citing works
Babaknejad, N., Nayeri, H., Hemmati, R., Bahrami, S., & Esmaillzadeh, A. (2018) · Hormone and Metabolic Research · doi:10.1055/a-0623-2909 · Cited by 70 · see citing works
Hepatic Glucagon Receptor Signaling Enhances Insulin-Stimulated Glucose Disposal in Rodents
Kim, T., Holleman, C. L., Nason, S. R., Arble, D. M., Ottaway, N., Chabenne, J. R., Loyd, C., Kim, J., Sandoval, D. A., Drucker, D. J., et al. (2018) · Diabetes · doi:10.2337/db18-0068 · Cited by 69 · see citing works
Self-citationHultman, K., Scarlett, J. M., Baquero, A. F., Cornea, A. M., Zhang, Y., Salinas, C. B. G., Brown, J. M., Morton, G. J., Whalen, E. J., Grove, K. L., et al. (2019) · The Journal of Comparative Neurology · doi:10.1002/cne.24668 · Cited by 65 · see citing works
Chen, M. Z., Chang, J. C., Zavala-Solorio, J., Kates, L., Thai, M., Ogasawara, A., Bai, X., Flanagan, S., Nunez, V., Phamluong, K., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.09.003 · Cited by 58 · see citing works
Somm, E., Henry, H., Bruce, S. J., Aeby, S., Rosikiewicz, M., Sykiotis, G. P., Asrih, M., Jornayvaz, F. R., Denechaud, P., Albrecht, U., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.91809 · Cited by 57 · see citing works
Rothberg, A. E., McEwen, L. N., Kraftson, A. T., Neshewat, G. M., Fowler, C. E., Burant, C., & Herman, W. H. (2013) · Quality of Life Research · doi:10.1007/s11136-013-0557-8 · Cited by 55 · see citing works
Pharmacological Approaches in the Treatment and Maintenance of Weight Loss
Gaal, L. V., & Dirinck, E. L. (2016) · Diabetes Care · doi:10.2337/dcs15-3016 · Cited by 53 · see citing works
Paul, J. R., Johnson, R. L., Jope, R. S., & Gamble, K. L. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.08.047 · Cited by 51 · see citing works
Self-citationMolecular elements in FGF19 and FGF21 defining KLB/FGFR activity and specificity
Agrawal, A., Parlee, S. D., Pérez–Tilve, D., Li, P., Pan, J. H., Mroz, P. A., Hansen, A. M. K., Andersen, B., Finan, B., Kharitonenkov, A., et al. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.05.003 · Cited by 42 · see citing works
Self-citationThe Nuclear Receptor Rev-erbα Regulates Adipose Tissue-specific FGF21 Signaling
Jager, J., Wang, F., Fang, B., Lim, H., Peed, L. C., Steger, D. J., Won, K., Kharitonenkov, A., Adams, A. C., & Lazar, M. A. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.719120 · Cited by 35 · see citing works
Self-citationFGF21 as a Therapeutic Reagent
Zhao, Y., Dunbar, J. D., & Kharitonenkov, A. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-0887-1_14 · Cited by 30 · see citing works
Self-citationGlucagon-Receptor Signaling Reverses Hepatic Steatosis Independent of Leptin Receptor Expression
Nason, S. R., Kim, T., ANTIPENKO, J. P., Finan, B., DiMarchi, R. D., Hunter, C. S., & Habegger, K. M. (2019) · Endocrinology · doi:10.1210/endocr/bqz013 · Cited by 26 · see citing works
Self-citationHansen, A. M. K., Vienberg, S. G., Lykkegaard, K., Zhao, X., Tingqing, G., Han, D., Zhang, X., Thøgersen, H., Sass‐Ørum, K., Tagmose, T. M., et al. (2018) · Biochemical Journal · doi:10.1042/bcj20180555 · Cited by 23 · see citing works
REV-ERBα regulates Fgf21 expression in the liver via hepatic nuclear factor 6
Chavan, R., Preitner, N., Okabe, T., Mansencal-Strittmatter, L., Xu, C., Ripperger, J. A., Pitteloud, N., & Albrecht, U. (2016) · Biology Open · doi:10.1242/bio.021519 · Cited by 21 · 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
Impact of weight loss on health-related quality of life
Bartlett, S. J., & Cheskin, L. J. (1999) · Cited by 17 · see citing works
炭水化物摂取を抑制する腹内側視床下部におけるグルタミン酸作動性ニューロンへのFGF21シグナル【JST・京大機械翻訳】
Sharon, O., Kyle, H. F., Kristin, E. C., Yavuz, Y., Sarah, A. S., Grant, C., Yuriy, M. U., Atasoy, D., Matthew, P., & Matthew, J. P. (2020) · Cell Metabolism · Cited by 15 · see citing works
Bethea, M. M., Liu, Y., Wade, A. K., Mullen, R. D., Gupta, R., Gelfanov, V. M., DiMarchi, R. D., Bhatnagar, S., Behringer, R. R., Habegger, K. M., et al. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00235.2018 · Cited by 14 · see citing works
Self-citationOptimization of Peptide Inhibitors of β-Klotho as Antagonists of Fibroblast Growth Factors 19 and 21
Pan, J. B., Parlee, S. D., Brunel, F. M., Li, P., Lu, W., Pérez–Tilve, D., Liu, F., Finan, B., Kharitonenkov, A., & DiMarchi, R. D. (2020) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.0c00100 · Cited by 9 · see citing works
Self-citation
Flagged first, then by citations
5 of the 81 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice
Knerr, P. J., Mowery, S. A., Douros, J. D., Premdjee, B., Hjøllund, K. R., He, Y., Kruse Hansen, A. M., Olsen, A. K., Perez-Tilve, D., DiMarchi, R. D., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101533 · Cited by 147 · see citing works
Self-citationNew developments in the biology of fibroblast growth factors
Ornitz, D. M., & Itoh, N. (2022) · WIREs Mechanisms of Disease · doi:10.1002/wsbm.1549 · Cited by 143 · see citing works
The molecular pharmacology of glucagon agonists in diabetes and obesity
Novikoff, A., & Müller, T. D. (2023) · Peptides · doi:10.1016/j.peptides.2023.171003 · Cited by 82 · see citing works
Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?
Conceição-Furber, E., Coskun, T., Sloop, K. W., & Samms, R. J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.868037 · Cited by 48 · see citing works
Cross Talk Between Insulin and Glucagon Receptor Signaling in the Hepatocyte
Habegger, K. M. (2022) · Diabetes · doi:10.2337/dbi22-0002 · Cited by 40 · see citing works
Self-citationLi, S., Zou, T., Chen, J., Li, J., & You, J. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.06.033 · Cited by 37 · see citing works
Elmelund, E., Galsgaard, K. D., Johansen, C. D., Trammell, S. A. J., Bomholt, A. B., Winther‐Sørensen, M., Hunt, J. E., Sørensen, C. M., Kruse, T., Lau, J. F., et al. (2022) · iScience · doi:10.1016/j.isci.2022.105296 · Cited by 32 · see citing works
Zhao, S., Yan, Z., Du, Y., Li, Z., Tang, C., Jing, L., Sun, L., Yang, Q., Tang, X., Yuan, Y., et al. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15860 · Cited by 30 · see citing works
Valdecantos, M. P., Ruiz, L., Folgueira, C., Rada, P., Gómez‐Santos, B., Solas, M., Hitos, A. B., Field, J., Francisco, V., Escalona-Garrido, C., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54080-w · Cited by 22 · see citing works
Oxyntomodulin physiology and its therapeutic development in obesity and associated complications
Kueh, M. T. W., Chong, M. C., Miras, A. D., & le Roux, C. W. (2024) · The Journal of Physiology · doi:10.1113/jp287407 · Cited by 19 · see citing works
Galsgaard, K. D., Elmelund, E., Johansen, C. D., Bomholt, A. B., Kizilkaya, H. S., Ceutz, F. R., Hunt, J. E., Kissow, H., Winther‐Sørensen, M., Sørensen, C. M., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101639 · Cited by 19 · see citing works
Wei, S., Li, C., Luo, X., Yang, L., Yu, L., Wang, Q., Meng, Z., Wang, T., & Chen, Y. (2021) · 中国科学通报:英文版 · doi:10.1016/j.scib.2021.12.024 · Cited by 16 · see citing works
Hope, D. C. D., & Tan, T. M.-M. (2023) · Peptides · doi:10.1016/j.peptides.2023.170962 · Cited by 16 · see citing works
Poly-Agonist Pharmacotherapies for Metabolic Diseases: Hopes and New Challenges
Allard, C., Cota, D., & Quarta, C. (2023) · Drugs · doi:10.1007/s40265-023-01982-6 · Cited by 15 · see citing works
Constitutively active glucagon receptor drives high blood glucose in birds
Zhang, C., Xiang, X., Liu, J., Huang, Y., Xue, J., Sun, Q., Leng, S., Liu, S., He, X., Hu, P., et al. (2025) · Nature · doi:10.1038/s41586-025-08811-8 · Cited by 14 · see citing works
Laker, R. C., Egolf, S., Will, S., Lantier, L., McGuinness, O. P., Brown, C. L., Bhagroo, N. V., Oldham, S. N., Kuszpit, K. K., Alfaro, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59773-4 · Cited by 13 · see citing works
Meroni, M., Dongiovanni, P., Tiano, F., Piciotti, R., Alisi, A., & Panera, N. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117608 · Cited by 13 · see citing works
RISING STARS: Targeting G protein-coupled receptors to regulate energy homeostasis
Jamaluddin, A., & Gorvin, C. M. (2023) · Journal of Molecular Endocrinology · doi:10.1530/jme-23-0014 · Cited by 11 · see citing works
Characterization of LY3324954 a long-acting glucagon-receptor agonist
Roell, W. C., Coşkun, T., Kim, T., O’Farrell, L. S., Martin, J. A., Nason, S. R., Hernandez-Alamillo, J., Dhantu, S., Drucker, D. J., Sloop, K. W., et al. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.102073 · Cited by 11 · see citing works
Self-citationCurrent Status of Therapeutic Peptides for the Management of Diabetes Mellitus
Prajapati, A., Rana, D., Rangra, S., Jindal, A. B., & Benival, D. M. (2024) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-024-10590-1 · Cited by 10 · see citing works
Nishida, K., Ueno, S., Seino, Y., Hidaka, S., Murao, N., Asano, Y., Fujisawa, H., Shibata, M., Takayanagi, T., Ohbayashi, K., et al. (2024) · Nutrients · doi:10.3390/nu16142270 · Cited by 9 · see citing works
Variable glucagon metabolic actions in diverse mouse models of obesity and type 2 diabetes
Wu, Y., Chan, A. Y., Hauke, J., Aung, O. H., Foollee, A., Cleofe, M. A. S., Stölting, H., Han, M., Jeppe, K. J., Barlow, C. K., et al. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.102064 · Cited by 9 · see citing works
CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects
Zheng, Y., Wang, Y., Xiong, X. B., Zhang, L., Zhu, J., Huang, B., Liu, X., Liu, J., Zhu, Z., Yang, G., et al. (2024) · Advanced Science · doi:10.1002/advs.202400819 · Cited by 6 · see citing works
Kim, T., Nason, S. R., ANTIPENKO, J. P., Finan, B., Shalev, A., DiMarchi, R. D., & Habegger, K. M. (2022) · Diabetes · doi:10.2337/db21-1018 · Cited by 6 · see citing works
Self-citationPancreatic hormones: insulin and glucagon
Litwack, G. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90262-5.00022-6 · Cited by 5 · see citing works
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 · see citing works
Kistkins, S., Moser, O., Ankudovičs, V., Bļizņuks, D., Mihailovs, T., Lobanovs, S., Sourij, H., Pfeiffer, A. F. H., & Pīrāgs, V. (2024) · Endocrine Connections · doi:10.1530/ec-23-0529 · Cited by 2 · see citing works
Glucagon-like peptide-1 receptor analogues and beyond: emerging obesity pharmacotherapies
Abburi, K., Melson, E., Miras, A. D., & Papamargaritis, D. (2025) · Panminerva Medica · doi:10.23736/s0031-0808.25.05339-x · Cited by 1 · see citing works
Avian GCGR-mediated continuous fat utilization offers perspectives for obesity treatment
Zhang, C., Wang, X. B., Feng, C., Zheng, H., Leng, S., Jiang, Y., Sun, Q., Li, X., Zhang, T., Zhang, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-66305-7 · Cited by 1 · see citing works
Kato, H., Yamaoka, I., & Kubota, H. (2026) · npj Systems Biology and Applications · doi:10.1038/s41540-026-00658-7 · Cited by 1 · see citing works
Deng, C.-X., Chen, Z.-M., Tang, Y.-X., Xi, Z.-X., Wang, S.-Y., Wu, H.-Y., Xu, B., & Xu, T.-C. (2026) · World Journal of Pharmacology · doi:10.5497/wjp.v15.i1.113080
Kaczynski, M., Zureikat, R. M., Kaczynski, M. R., Sitarz, R., & Karakuła‐Juchnowicz, H. (2026) · Biomedicines · doi:10.3390/biomedicines14091957
Popa, E., Popa, A. E., Poroch, V., Schreiner, T. G., Slănină, A. M., Poroch, M., Hatneanu, A. M., Ungureanu, M. I., Petroaie, A. D., Bacușcă, A. I., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198738
- Authors
- Nason, S. R., Antipenko, J., Presedo, N., Cunningham, S. E., Pierre, T. H., Kim, T., Paul, J. R., Holleman, C., Young, M. E., Gamble, K. L., Finan, B., DiMarchi, R., Hunter, C. S., Kharitonenkov, A., & Habegger, K. M.
- Affiliations
- Comprehensive Diabetes Center and Division of Endocrinology, Diabetes and Metabolism, Department of Medicine,
- Department of Psychiatry and Behavioral Neurobiology, and
- University of Alabama at Birmingham (US)
- Novo Nordisk Research Center Indianapolis, Inc., Indianapolis, Indiana, USA.
- Indiana University Bloomington (US)
- AK Biotechnologies LLC, Zionsville, Indiana, USA.
- Corresponding author
- Habegger, Kirk M.
- ORCID
- Venue
- JCI Insight
- Published
- 2021-02-22
- Volume
- 6
- Issue
- 4
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC7934938
- OpenAlex
- W3118898040
- Cited by
- 34
- References
- 81
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 10 · 2023: 5 · 2022: 9 · 2021: 2
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- JCI Insight (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (1R01DK112934,P30DK079626,T32HL105349)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- glucagon receptor agonist, weight loss, KLB, β-Klotho, FGF21, central nervous system, obesity treatment, metabolic syndrome, serum cholesterol, hepatic triglycerides
- MeSH terms
- Klotho Proteins, Animals, Body Weight, Eating, Fibroblast Growth Factors, Glucagon, Glucose, Homeostasis, Liver, Male, Mice, Inbred C57BL, Obesity, Peptides, Signal Transduction, Weight Loss, Gene Expression, Receptors, Glucagon, Mice, Knockout, Lipid Metabolism, 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