FGF21 Lowers Plasma Triglycerides by Accelerating Lipoprotein Catabolism in White and Brown Adipose Tissues
Open accessAbstract
FGF21 decreases plasma triglycerides (TGs) in rodents and humans; however, the underlying mechanism or mechanisms are unclear. In the present study, we examined the role of FGF21 in production and disposal of TG-rich lipoproteins (TRLs) in mice. Treatment with pharmacological doses of FGF21 acutely reduced plasma non-esterified fatty acids (NEFAs), liver TG content, and VLDL-TG secretion. In addition, metabolic turnover studies revealed that FGF21 facilitated the catabolism of TRL in white adipose tissue (WAT) and brown adipose tissue (BAT). FGF21-dependent TRL processing was strongly attenuated in CD36-deficient mice and transgenic mice lacking lipoprotein lipase in adipose tissues. Insulin resistance in diet-induced obese and ob/ob mice shifted FGF21 responses from WAT toward energy-combusting BAT. In conclusion, FGF21 lowers plasma TGs through a dual mechanism: first, by reducing NEFA plasma levels and consequently hepatic VLDL lipidation and, second, by increasing CD36 and LPL-dependent TRL disposal in WAT and BAT.
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?
FGF21's triglyceride-lowering effects are mediated by altered adipose and liver metabolism: accelerated lipoprotein catabolism, suppression of postprandial lipolysis, decreased hepatic ER and oxidative stress, and increased beta-oxidation of lipids in the liver.
“Pharmacological administration of FGF21 or FGF21 analogues exerts lipid-lowering effects through accelerated lipoprotein catabolism108, suppression of postprandial lipolysis in adipose tissues88, decreased hepatic endoplasmic reticulum and oxidative stress109,110, and increased beta-oxidation of lipids in the liver62”
From Metabolic messengers: FGF21 (2021) · cites this paper as [108]
The potent effects of FGF21 on lipid metabolism are also present in adipose-specific Klb knockout mice.
“In addition, the potent effects of FGF21 on lipid metabolism (115) are also present in adipose-specific Klb knockout mice (11).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [115]
Cites
Brown Adipose Tissue: Function and Physiological Significance
CANNON, B., & NEDERGAARD, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00015.2003 · Cited by 6,433 · 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
Brown adipose tissue activity controls triglyceride clearance
Bartelt, A., Bruns, O. T., Reimer, R., Hohenberg, H., Ittrich, H., Peldschus, K., Kaul, M. G., Tromsdorf, U. I., Weller, H., Waurisch, C., et al. (2011) · Nature Medicine · doi:10.1038/nm.2297 · Cited by 1,608 · see citing works
Self-citationBadman, 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
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
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
Ouellet, V., Labbé, S. M., Blondin, D. P., Phoenix, S., Guérin, B., Haman, F., Turcotte, É. E., Richard, D., & Carpentier, A. C. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60433 · Cited by 985 · see citing works
The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes
Gaich, G., Chien, J. Y., Fu, H., Glass, L. C., Deeg, M. A., Holland, W. L., Kharitonenkov, A., Bumol, T., Schilske, H. K., & Moller, D. E. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.005 · Cited by 885 · see citing works
Lipoprotein lipase: from gene to obesity
Wang, H., & Eckel, R. H. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90920.2008 · Cited by 862 · see citing works
Obesity Is a Fibroblast Growth Factor 21 (FGF21)-Resistant State
Fisher, F. M., Chui, P. C., Antonellis, P. J., Bina, H. A., Kharitonenkov, A., Flier, J. S., & Maratos-Flier, E. (2010) · Diabetes · doi:10.2337/db10-0193 · Cited by 830 · see citing works
Adiels, M., Olofsson, S.-O., Taskinen, M.-R., & Borén, J. (2008) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.160192 · Cited by 820 · see citing works
Kurosu, H., Choi, M., Ogawa, Y., Dickson, A. S., Goetz, R., Eliseenkova, A. V., Mohammadi, M., Rosenblatt, K. P., Kliewer, S. A., & Kuro-o, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704165200 · Cited by 748 · 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
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
Lin, Z., Tian, H., Lam, K. S. L., Lin, S., Hoo, R. C. L., Konishi, M., Itoh, N., Wang, Y., Bornstein, S. R., Xu, A., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.005 · Cited by 691 · see citing works
Physiological regulation of lipoprotein lipase
Kersten, S. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.03.013 · Cited by 548 · 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
An FGF21-Adiponectin-Ceramide Axis Controls Energy Expenditure and Insulin Action in Mice
Holland, W., Adams, A., Brozinick, J., Bui, H., Miyauchi, Y., Kusminski, C., Bauer, S., Wade, M., Singhal, E., Cheng, C. C., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.019 · Cited by 525 · 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
Increased very low density lipoprotein (VLDL) secretion, hepatic steatosis, and insulin resistance
Choi, S. H., & Ginsberg, H. N. (2011) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2011.04.007 · Cited by 418 · see citing works
Cellular fatty acid uptake: a pathway under construction
Su, X., & Abumrad, N. A. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2008.11.001 · Cited by 410 · 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
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
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
FATP1 Is an Insulin-Sensitive Fatty Acid Transporter Involved in Diet-Induced Obesity
Wu, Q., Ortegon, A. M., Tsang, B., Doege, H., Feingold, K. R., & Stahl, A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.9.3455-3467.2006 · Cited by 296 · see citing works
Merkel, M., Loeffler, B., Kluger, M. A., Fabig, N., Geppert, G., Pennacchio, L. A., Laatsch, A., & Heeren, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411412200 · Cited by 292 · see citing works
Self-citationSarruf, 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
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
Barrows, B. R., & Parks, E. J. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1709 · Cited by 273 · 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
Fisher, F. M., Chui, P. C., Nasser, I. A., Popov, Y., Cunniff, J. C., Lundasen, T., Kharitonenkov, A., Schuppan, D., Flier, J. S., & Maratos-Flier, E. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.07.044 · Cited by 263 · see citing works
Interplay between FGF21 and insulin action in the liver regulates metabolism
Emanuelli, B., Vienberg, S. G., Smyth, G., Cheng, C., Stanford, K. I., Arumugam, M., Michael, M. D., Adams, A. C., Kharitonenkov, A., & Kahn, C. R. (2014) · Journal of Clinical Investigation · doi:10.1172/jci67353 · Cited by 243 · see citing works
Long-chain fatty acid uptake and FAT/CD36 translocation in heart and skeletal muscle
Koonen, D. P. Y., Glatz, J. F. C., Bonen, A., & Luiken, J. J. F. P. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2005.08.018 · Cited by 238 · see citing works
Lipotoxicity in type 2 diabetic cardiomyopathy
van de Weijer, T., Schrauwen‐Hinderling, V. B., & Schrauwen, P. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr212 · Cited by 235 · see citing works
Cellular 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
Human Brown Adipose Tissue: What We Have Learned So Far
Betz, M. J., & Enerbäck, S. (2015) · Diabetes · doi:10.2337/db15-0146 · Cited by 223 · see citing works
Blondin, D. P., Labbé, S. M., Noll, C., Kunach, M., Phoenix, S., Guérin, B., Turcotte, É. E., Haman, F., Richard, D., & Carpentier, A. C. (2015) · Diabetes · doi:10.2337/db14-1651 · Cited by 219 · see citing works
Foltz, I. N., Hu, S., King, C., Wu, X., Yang, C., Wang, W., Weiszmann, J., Stevens, J., Chen, J. S., Nuanmanee, N., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004690 · Cited by 211 · see citing works
Pharmacologic Effects of FGF21 Are Independent of the “Browning” of White Adipose Tissue
Véniant, M. M., Sivits, G., Helmering, J., Komorowski, R., Lee, J., Fan, W., Moyer, C., & Lloyd, D. J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.04.019 · Cited by 204 · 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
Molecular processes that handle — and mishandle — dietary lipids
Williams, K. J. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35206 · Cited by 161 · 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
Long-Acting FGF21 Has Enhanced Efficacy in Diet-Induced Obese Mice and in Obese Rhesus Monkeys
Véniant, M. M., Komorowski, R., Chen, P., Stanislaus, S., Winters, K., Hager, T., Zhou, L., Wada, R., Hecht, R. I., & Xu, J. (2012) · Endocrinology · doi:10.1210/en.2012-1211 · Cited by 147 · see citing works
Role of the type 2 iodothyronine deiodinase (D2) in the control of thyroid hormone signaling
Drigo, R. A. E., Fonseca, T. L., Werneck‐de‐Castro, J. P., & Bianco, A. C. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2012.08.019 · Cited by 146 · see citing works
FGF21 Promotes Metabolic Homeostasis via White Adipose and Leptin in Mice
Véniant, M. M., Hale, C., Helmering, J., Chen, M. M., Stanislaus, S., Busby, J., Vonderfecht, S., Xu, J., & Lloyd, D. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040164 · Cited by 141 · see citing works
Effect of Triton on Lipoprotein Lipase of Rat Plasma
Schotz, M. C., Scanu, A. M., & Page, I. H. (1957) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1957.188.2.399 · Cited by 128 · see citing works
Huang, J., Ishino, T., Chen, G., Rolzin, P., Osothprarop, T. F., Retting, K., Li, L., Jin, P., Matin, M. J., Huyghe, B., et al. (2013) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.204420 · Cited by 121 · see citing works
Self-citationLi, X., Ge, H., Weiszmann, J., Hecht, R. I., Li, Y., Véniant, M. M., Xu, J., Wu, X., Lindberg, R. A., & Li, Y. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.09.012 · Cited by 107 · see citing works
Camporez, J. P., Kanda, S., Petersen, M. C., Jornayvaz, F. R., Samuel, V. T., Bhanot, S., Petersen, K. F., Jurczak, M. J., & Shulman, G. I. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m054080 · Cited by 60 · see citing works
Effects of adipocyte lipoprotein lipase on de novo lipogenesis and white adipose tissue browning
Bartelt, A., Weigelt, C., Cherradi, M. L., Niemeier, A., Tödter, K., Heeren, J., & Scheja, L. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.11.011 · Cited by 59 · see citing works
Self-citationJochen, A., & Hays, J. (1993) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)35741-2 · Cited by 49 · see citing works
Lee, D. V., Li, D., Yan, Q., Zhu, Y., Goodwin, B. J., Calle, R. A., Brenner, M. B., & Talukdar, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111767 · Cited by 38 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028 · see citing works
The endocrine function of adipose tissues in health and cardiometabolic disease
Scheja, L., & Heeren, J. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0230-6 · Cited by 663 · see citing works
Self-citationThe 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
The Liver as an Endocrine Organ—Linking NAFLD and Insulin Resistance
Watt, M. J., Miotto, P. M., De Nardo, W., & Montgomery, M. K. (2019) · Endocrine Reviews · doi:10.1210/er.2019-00034 · Cited by 615 · see citing works
Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy
Chiang, J. Y. L., & Ferrell, J. M. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00223.2019 · Cited by 580 · see citing works
The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue
Lynes, M. D., Leiria, L. O., Lundh, M., Bartelt, A., Shamsi, F., Huang, T. L., Takahashi, H., Hirshman, M. F., Schlein, C., Lee, A., et al. (2017) · Nature Medicine · doi:10.1038/nm.4297 · Cited by 452 · see citing works
“In adipocytes, FA uptake is mediated in part by a diverse family of FA transport proteins, including CD36 and fatty acid transport protein 1 (FATP1), both of which are hormone-sensitive FA transporters 26,29 required for nonshivering thermogenesis in mice 30,31 .”
Self-citationHypertriglyceridaemia and risk of coronary artery disease
Reiner, Ž. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.31 · Cited by 386 · 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
“In addition, these data demonstrate that the potent triglyceride-lowering effects of FGF21 through accelerated lipoprotein catabolism in white and brown adipose tissues (Schlein et al., 2016) are not mediated by direct signaling to adipose tissues.”
Worthmann, A., John, C., Rühlemann, M. C., Baguhl, M., Heinsen, F.-A., Schaltenberg, N., Heine, M., Schlein, C., Evangelakos, I., Mineo, C., et al. (2017) · Nature Medicine · doi:10.1038/nm.4357 · Cited by 318 · see citing works
Self-citationFlippo, K. H., & Potthoff, M. J. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00354-2 · Cited by 311 · see citing works
Gao, Y., Zhang, W., Zeng, L.-Q., Bai, H., Li, J., Zhou, J., Zhou, G., Fang, C., Wang, F., & Qin, X.-J. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101635 · Cited by 293 · see citing works
Treatment of type 2 diabetes: challenges, hopes, and anticipated successes
Nauck, M. A., Wefers, J., & Meier, J. J. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00113-3 · Cited by 300 · see citing works
A Dozen Years of Discovery: Insights into the Physiology and Pharmacology of FGF21
Kliewer, S. A., & Mangelsdorf, D. J. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.004 · Cited by 273 · see citing works
“In mice, FG21 lowers plasma triglycerides by reducing non-esterified fatty acids and by increasing lipoprotein catabolism in white and brown adipose tissue (Schlein et al., 2016).”
BackgroundFibroblast 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
Brown Adipose Tissue: an Update on Recent Findings
Marlatt, K. L., & Ravussin, É. (2017) · Current Obesity Reports · doi:10.1007/s13679-017-0283-6 · Cited by 234 · see citing works
Induction of Adipose Tissue Browning as a Strategy to Combat Obesity
Kuryłowicz, A., & Puzianowska-Kuźnicka, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176241 · Cited by 219 · see citing works
“In turn, FGF21 knockout reduces the ability to adapt to chronic cold exposure with diminished browning of WAT in mice [101].”
BackgroundMachado, S. A., Pasquarelli-do-Nascimento, G., da Silva, D. S., Farias, G. R., Santos, I. D. O., Baptista, L. B., & Magalhães, K. G. (2022) · Nutrition & Metabolism · doi:10.1186/s12986-022-00694-0 · Cited by 229 · see citing works
“Moreover, studies show that the increase in brite and brown adipocytes in WAT leads to an elevation in lipoprotein lipase (LPL) activity and subsequently an increase in circulating lipids available for BAT through intravascular hydrolysis of chylomicron triglycerides [248].”
BackgroundFibroblast 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
Tillman, E. J., & Rolph, T. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.601290 · Cited by 209 · see citing works
Hepatic NADH reductive stress underlies common variation in metabolic traits
Goodman, R. P., Markhard, A. L., Shah, H., Sharma, R., Skinner, O. S., Clish, C. B., Deik, A., Patgiri, A., Hsu, Y.-H. H., Masia, R., et al. (2020) · Nature · doi:10.1038/s41586-020-2337-2 · Cited by 207 · see citing works
Brown Adipose Tissue—A Translational Perspective
Carpentier, A. C., Blondin, D. P., Haman, F., & Richard, D. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac015 · Cited by 202 · see citing works
Yamashita, S., Masuda, D., & Matsuzawa, Y. (2020) · Current Atherosclerosis Reports · doi:10.1007/s11883-020-0823-5 · Cited by 191 · see citing works
Heine, M., Fischer, A. W., Schlein, C., Jung, C., Straub, L. G., Gottschling, K., Mangels, N., Yuan, Y., Nilsson, S. K., Liebscher, G., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.020 · Cited by 178 · see citing works
Self-citationFGF Family: From Drug Development to Clinical Application
Hui, Q., Jin, Z., Li, X., Liu, C., & Wang, X. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19071875 · Cited by 182 · see citing works
Harrison, S. A., Rolph, T., Knott, M., & Dubourg, J. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.034 · Cited by 176 · see citing works
Iizuka, K., Takao, K., & Yabe, D. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.587189 · Cited by 152 · see citing works
FGF21: A Novel Regulator of Glucose and Lipid Metabolism and Whole-Body Energy Balance
Szczepańska, E., & Gietka‐Czernel, M. (2022) · Hormone and Metabolic Research · doi:10.1055/a-1778-4159 · Cited by 155 · see citing works
“Moreover, FGF21 lowers serum TG levels through suppression of WAT lipolysis [9] and increases in lipoprotein lipase activity and lipoprotein catabolism [60].”
BackgroundFruchart, J.-C., Santos, R. D., Aguilar-Salinas, C., Aikawa, M., Al Rasadi, K., Amarenco, P., Barter, P. J., Ceska, R., Corsini, A., Després, J.-P., et al. (2019) · Cardiovascular Diabetology · doi:10.1186/s12933-019-0864-7 · Cited by 140 · see citing works
Kim, A. M., Somayaji, V. R., Dong, J. Q., Rolph, T. P., Weng, Y., Chabot, J. R., Gropp, K. E., Talukdar, S., & Calle, R. A. (2017) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13023 · Cited by 145 · see citing works
Self-citationFibroblast growth factor 21 in non-alcoholic fatty liver disease
Tucker, B., Li, H., Long, X., Rye, K., & Ong, K. L. (2019) · Metabolism · doi:10.1016/j.metabol.2019.153994 · Cited by 132 · see citing works
Adipose tissue browning in mice and humans
Herz, C. T., & Kiefer, F. W. (2019) · Journal of Endocrinology · doi:10.1530/joe-18-0598 · Cited by 135 · see citing works
Wanders, 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
“Together these findings illustrate that FGF21 is an essential mediator of the transcriptional programs induced by dietary MR in BAT and WAT.”
BackgroundInfluentialKaufman, A., Abuqayyas, L., Denney, W. S., Tillman, E. J., & Rolph, T. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100057 · Cited by 131 · see citing works
“Geo mean fasting IGF-1, ng/mL (% CV) 135 (47) 155 (29) 114 (29) 156 (20) 113 (33) 147 (32) 164 (38) 129 (47) 112 (53) 183 (36)”
Understanding bile acid signaling in diabetes: From pathophysiology to therapeutic targets
Ferrell, J. M., & Chiang, J. Y. L. (2019) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2019.0043 · Cited by 139 · see citing works
Mechanisms by Which Skeletal Muscle Myokines Ameliorate Insulin Resistance
Balakrishnan, R., & Thurmond, D. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094636 · Cited by 132 · see citing works
“FGF21 Adipose tissue, Liver ↑ Insulin sensitivity [59,177] ↑ Lipolysis [178,179] ↑ Oxidative capacities [180] ↓ Triglycerides l [181,182]”
BackgroundCaputo, T., Gilardi, F., & Desvergne, B. (2017) · FEBS Letters · doi:10.1002/1873-3468.12742 · Cited by 111 · see citing works
Human Brown Adipose Tissue and Metabolic Health: Potential for Therapeutic Avenues
Singh, R., Barrios, A., Dirakvand, G., & Pervin, S. (2021) · Cells · doi:10.3390/cells10113030 · Cited by 109 · see citing works
Fibroblast 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
Microbial Metabolites: Critical Regulators in NAFLD
Dai, X., Hou, H., Zhang, W., Liu, T., Li, Y., Wang, S., Wang, B., & Cao, H. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.567654 · Cited by 102 · see citing works
CREBH Regulates Systemic Glucose and Lipid Metabolism
Nakagawa, Y., & Shimano, H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051396 · Cited by 97 · see citing works
“CREBH also regulates FGF21 [9], which stimulates LPL-mediated TG clearance [95], thereby contributing to hypertriglyceridemia in CREBH KO mice.”
BackgroundThe role of FGF21 and its analogs on liver associated diseases
Falamarzi, K., Malekpour, M., Tafti, M. F., Azarpira, N., Behboodi, M., & Zarei, M. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.967375 · Cited by 94 · see citing works
“FGF21 could also decrease postprandial triglycerides (TGs) and facilitate fatty acid storage in adipose tissue (40).”
BackgroundBrown adipose tissue and lipid metabolism
Heeren, J., & Scheja, L. (2018) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000504 · Cited by 95 · see citing works
Self-citationCold and Exercise: Therapeutic Tools to Activate Brown Adipose Tissue and Combat Obesity
da Silva, C. P. V., Hernández‐Saavedra, D., White, J. D., & Stanford, K. (2019) · Biology · doi:10.3390/biology8010009 · Cited by 95 · see citing works
“FGF21 effects in BAT include acutely enhancing in insulin sensitivity, glucose uptake, and accelerated lipoprotein catabolism [110,114,115].”
BackgroundHenriksson, E., & Andersen, B. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.601349 · Cited by 95 · see citing works
“The accumulation of hepatic fat in the FGF21 ko may be linked to an increased flux of FFA from the adipose tissue (98) but may also be caused by a reduction in hepatic b-oxidation due to higher plasma insulin (99) and reduced TG uptake (65) and storage in the adipose tissue.”
BackgroundUpdate on dyslipidemia in hypothyroidism: the mechanism of dyslipidemia in hypothyroidism
Liu, H., & Peng, D. (2022) · Endocrine Connections · doi:10.1530/ec-21-0002 · Cited by 101 · see citing works
“FGF21 reduces circulating FFAs by inhibiting lipolysis in white adipose tissue (WAT) (69) and stimulating FFAs uptake into WAT, consequently decreasing the secretion of VLDL in liver (70).”
Dyslipidemia in retinal metabolic disorders
Fu, Z., Chen, C. T., Cagnone, G., Heckel, É., Sun, Y., Cakir, B., Tomita, Y., Huang, S., Li, Q., Britton, W. R., et al. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201910473 · Cited by 92 · see citing works
“In obese type 2 diabetic mice, FGF21 lowers plasma triglycerides by lipoprotein catabolism in adipose tissue and maintains adipocyte phospholipid homeostasis (Foltz et al, 2012; Schlein et al, 2016; Ye et al, 2016; Stanislaus et al, 2017).”
BackgroundLoss of CTRP1 disrupts glucose and lipid homeostasis
Rodriguez, S., Lei, X., Petersen, P. S., Tan, S. Y., Little, H. C., & Wong, G. W. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00087.2016 · Cited by 88 · see citing works
Impact of dietary carbohydrate type and protein–carbohydrate interaction on metabolic health
Wali, J. A., Milner, A. J., Luk, A. W. S., Pulpitel, T., Dodgson, T., Facey, H. J. W., Wahl, D., Kebede, M. A., Senior, A. M., Sullivan, M. A., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00393-9 · Cited by 86 · see citing works
Liu, C., Schönke, M., Zhou, E., Li, Z., Kooijman, S., Boon, M. R., Larsson, M., Wallenius, K., Dekker, N., Barlind, L., et al. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab076 · Cited by 81 · see citing works
“FGF21 was recently shown to directly and indirectly (via the sympathetic nervous system) act on adipose tissue to promote brown fat activation and white fat browning, thereby increasing energy expenditure and promoting weight loss.(17,18) Studies on the role of FGF21 in atherosclerosis development are still scarce and…”
BackgroundResultEndogenous FGF21-signaling controls paradoxical obesity resistance of UCP1-deficient mice
Keipert, S., Lutter, D., Schroeder, B. O., Brandt, D., Ståhlman, M., Schwarzmayr, T., Graf, E., Fuchs, H., de Angelis, M. H., Tschöp, M. H., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14069-2 · Cited by 82 · see citing works
FGF19 and FGF21: In NASH we trust
Talukdar, S., & Kharitonenkov, A. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101152 · Cited by 82 · see citing works
“In a 12-week phase 2 study, QD and QW administration of Pegbelfermin in patients with obesity and type 2 diabetes caused significant increase in HDLc and decrease in TGs.”
BackgroundInfluentialSelf-citationThe significance of beige and brown fat in humans
Kiefer, F. W. (2017) · Endocrine Connections · doi:10.1530/ec-17-0037 · Cited by 79 · see citing works
Fischer, A. W., Cannon, B., & Nedergaard, J. (2019) · Endocrine Reviews · doi:10.1210/endrev/bnz016 · Cited by 79 · see citing works
Self-citationAdipokines in obesity and metabolic-related-diseases
Pestel, J., Blangero, F., Watson, J., Pirola, L., & Eljaafari, A. (2023) · Biochimie · doi:10.1016/j.biochi.2023.04.008 · Cited by 80 · see citing works
Auer, M. K., Ebert, T., Pietzner, M., Defreyne, J., Fuss, J., Stalla, G. K., & T’Sjoen, G. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01559 · Cited by 75 · see citing works
“Previous studies have revealed that hypoadiponectinemia is an independent risk factor for arterial hypertension (27).”
BackgroundThe potential function and clinical application of FGF21 in metabolic diseases
Chen, Z., Yang, L., Liu, Y., Huang, P., Song, H., & Zheng, P. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1089214 · Cited by 72 · see citing works
“, 2005) and lipid (Schlein et al., 2016), and lipogenesis in adipose tissues (Dutchak et al.”
BackgroundLiu, C., Schönke, M., Spoorenberg, B., Lambooij, J. M., van der Zande, H. J. P., Zhou, E., Tushuizen, M. E., Andréasson, A., Park, A., Oldham, S. N., et al. (2023) · eLife · doi:10.7554/elife.83075 · Cited by 72 · see citing works
CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis
Park, J., Xu, X., Cho, S., Hur, K. Y., Lee, M., Kersten, S., & Lee, A. (2016) · Scientific Reports · doi:10.1038/srep27938 · Cited by 71 · see citing works
Rader, D. J., Maratos-Flier, E., Nguyen, A., Hom, D., Ferriere, M., Li, Y., Kompa, J., Martic, M., Hinder, M., Basson, C. T., et al. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab624 · Cited by 72 · 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
Jin, L., Yang, R., Geng, L., & Xu, A. (2023) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-032322-093904 · Cited by 71 · see citing works
Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use
Worthmann, A., Ridder, J., Piel, S., Evangelakos, I., Musfeldt, M., Voß, H., O’Farrell, M., Fischer, A. W., Adak, S., Sundd, M., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-44364-y · Cited by 69 · see citing works
Self-citationFGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue
Markan, K. R., Naber, M. C., Small, S. M., Peltekian, L., Kessler, R. L., & Potthoff, M. J. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.03.009 · Cited by 68 · see citing works
“Indeed, a recent publication demonstrated that acute FGF21 administration promotes lipid uptake in white adipose tissue under lean conditions, but redirects lipid catabolism to brown adipose tissue during obese conditions [37].”
BackgroundFischer, A. W., Jaeckstein, M. Y., Gottschling, K., Heine, M., Sass, F., Mangels, N., Schlein, C., Worthmann, A., Bruns†, O. T., Yuan, Y., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.12.001 · Cited by 67 · see citing works
“Of note, we previously showed that thermogenically activated BAT and WAT internalize entire TRL particles (Bartelt et al., 2011; Heine et al., 2018; Schlein et al., 2016) in a process that does not depend on low-density lipoproteins (LDL) receptors or apolipoprotein E (Bartelt et al.”
BackgroundSelf-citationFGF21 Administration Suppresses Retinal and Choroidal Neovascularization in Mice
Fu, Z., Gong, Y. Q., Liegl, R. G.-H., Wang, Z., Liu, C., Meng, S. S., Burnim, S. B., Saba, N. J., Fredrick, T. W., Morss, P., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.01.014 · Cited by 66 · see citing works
“FGF21 treatment decreases body weight and improves the lipid profile (decreases triglycerides and increases high-density lipoprotein [HDL] cholesterol levels) in type 2 diabetes patients, nonhuman primates, and obese rodents (Bernardo et al., 2015; Gaich et al., 2013; Schlein et al., 2016; Talukdar et al., 2016), sugg…”
Self-citationYamashita, S., Masuda, D., & Matsuzawa, Y. (2019) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.48918 · Cited by 68 · see citing works
Nishida, K., Kinoshita, S., Yokoi, N., Kaneda, M., Hashimoto, K., & Yamamoto, S. (1994) · PubMed · Cited by 66 · see citing works
Adipokines from white adipose tissue in regulation of whole body energy homeostasis
Sahu, B., & Bal, N. C. (2022) · Biochimie · doi:10.1016/j.biochi.2022.09.003 · Cited by 69 · see citing works
Mottillo, E. P., Desjardins, E. M., Fritzen, A. M., Zou, V. Z., Crane, J. D., Yabut, J. M., Kiens, B., Erion, D. M., Lanba, A., Granneman, J. G., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.04.001 · Cited by 57 · see citing works
“These effects have been related to increases in glucose uptake and triglyceride clearance in white (WAT) and brown adipose tissue (BAT) [10] and require the expression of the FGF21 receptor, fibroblast growth factor receptor 1c (FGFR1c), and cofactor beta klotho (KLB) [11,12].”
BackgroundSelf-citationLee, Y.-H., Kim, S. H., Kim, S.-N., Kwon, H.-J., Kim, J.-D., Oh, J. Y., & Jung, Y.-S. (2016) · Oncotarget · doi:10.18632/oncotarget.10506 · Cited by 57 · see citing works
“Genetic overexpression FGF21 or pharmacological treatment of FGF21 can correct glucose and lipid metabolism [39] and has beneficial effects in mouse models of obesity [38, 40].”
BackgroundPPAR-α agonists are still on the rise: an update on clinical and experimental findings
Ferri, N., Corsini, A., Sirtori, C. R., & Ruscica, M. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1312339 · Cited by 56 · see citing works
“increasing lipoprotein disposal by way of LPL and CD36 [61].”
BackgroundFamilial Combined Hyperlipidemia: Current Knowledge, Perspectives, and Controversies
Bello‐Chavolla, O. Y., Kuri-García, A., Ríos-Ríos, M., Vargas‐Vázquez, A., Cortés-Arroyo, J. E., Tapia-González, G., Cruz‐Bautista, I., & Aguilar-Salinas, C. A. (2018) · Revista de investigaci�n Cl�nica · doi:10.24875/ric.18002575 · Cited by 59 · see citing works
Dietary Methionine Restriction Reduces Inflammation Independent of FGF21 Action
Sharma, S., Dixon, T., Jung, S., Graff, E. C., Forney, L. A., Gettys, T. W., & Wanders, D. (2019) · Obesity · doi:10.1002/oby.22534 · Cited by 54 · see citing works
“Others showed that the FGF21-induced reduction in hepatic triglycerides was due to FGF21 action on adipocytes, limiting the fatty acid supply and triglyceride content in liver (44).”
BackgroundSenp2 regulates adipose lipid storage by de-SUMOylation of Setdb1
Zheng, Q., Cao, Y., Chen, Y., Wang, J., Fan, Q., Huang, X., Wang, Y., Wang, T., Wang, X., Ma, J., et al. (2017) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjx055 · Cited by 53 · see citing works
Contributions of White and Brown Adipose Tissues to the Circadian Regulation of Energy Metabolism
Heyde, I., Begemann, K., & Oster, H. (2021) · Endocrinology · doi:10.1210/endocr/bqab009 · Cited by 54 · see citing works
“Conversely, in insulin-resistant obese mice, FGF21 increases catabolism of TGs in BAT while inducing WAT browning by an increase in PGC-1α protein levels (51-53).”
BackgroundTrevino-Villarreal, J. H., Reynolds, J. S., Bartelt, A., Langston, P. K., MacArthur, M. R., Arduini, A., Tosti, V., Veronese, N., Bertozzi, B., Brace, L. E., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.99470 · Cited by 50 · see citing works
“Like APOA5, FGF21 is elevated upon PR (20, 52) — as well as in response to sugar (53) — and has an established role in promoting TG clearance via activation of white and brown adipose tissue (43) and increasing energy expenditure via central and peripheral mechanisms — for example, through increased”
BackgroundSelf-citationGliniak, C. M., Gordillo, R., Youm, Y., Lin, Q., Crewe, C., Zhang, Z., Field, B. C., Fujikawa, T., Virostek, M., Zhao, S., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.05.011 · Cited by 53 · see citing works
Polysaccharides: The Potential Prebiotics for Metabolic Associated Fatty Liver Disease (MAFLD)
Guo, Q., Li, Y., Dai, X., Wang, B., Zhang, J., & Cao, H. (2023) · Nutrients · doi:10.3390/nu15173722 · Cited by 50 · see citing works
Ferdous, S.-E., & Ferrell, J. M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168731 · Cited by 49 · see citing works
“FGF21 also prevents mTORC1 signaling to upregulate insulin signaling [23–25].”
BackgroundThe Origins, Evolution, and Future of Dietary Methionine Restriction
Fang, H., Stone, K. P., Wanders, D., Forney, L. A., & Gettys, T. W. (2022) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-062320-111849 · Cited by 47 · see citing works
de Urturi, D. S., Buqué, X., Porteiro, B., Folgueira, C., Mora, A., Delgado, T. C., Prieto‐Fernández, E., Olaizola, P., Gómez‐Santos, B., Apodaka‐Biguri, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28749-z · Cited by 48 · see citing works
Mechanisms of microplastics on gastrointestinal injury and liver metabolism disorder (Review)
Zhou, L. Q., Ran, L., He, Y., & Huang, Y. (2025) · Molecular Medicine Reports · doi:10.3892/mmr.2025.13463 · Cited by 48 · see citing works
“Thus, plasma triglycerides build up, leading to an increased risk of hyperlipidemia in humans (71,72).”
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
Ying, Z., Tramper, N., Zhou, E., Boon, M. R., Rensen, P. C. N., & Kooijman, S. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac131 · Cited by 43 · see citing works
“Firstly, treatment of mice with recombinant human FGF21 enhanced the uptake of glucose(101) and triglyceride-derived FAs from TRLs(102) by BAT and promoted WAT browning,(101,102) which normalized glycaemia(101) and reduced plasma triglycerides.(102) Furthermore, FGF21-stimulated lipolysis of TRLs by BAT consequently s…”
BackgroundMaurer, S. F., Fromme, T., Mocek, S., Zimmermann, A., & Klingenspor, M. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00121.2019 · Cited by 42 · see citing works
Metabolic determinants of Alzheimer’s disease: A focus on thermoregulation
Tournissac, M., Leclerc, M., Valentin‐Escalera, J., Vandal, M., Bosoi, C. R., Planel, E., & Calon, F. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101462 · Cited by 41 · see citing works
ChREBP Reciprocally Regulates Liver and Plasma Triacylglycerol Levels in Different Manners
Iizuka, K., Takao, K., Kato, T., Horikawa, Y., & Takeda, J. (2018) · Nutrients · doi:10.3390/nu10111699 · Cited by 41 · see citing works
“Angptl3 is known to increase lipolysis by inhibiting lipoprotein lipase [20] and Fgf21 is known to promote TAG disposal in adipose tissues [19].”
BackgroundAl-Mrabeh, A. H. (2021) · Biomedicines · doi:10.3390/biomedicines9020226 · Cited by 42 · see citing works
Severe hypertriglyceridemia: Existing and emerging therapies
Malick, W. A., Do, R., & Rosenson, R. S. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108544 · Cited by 44 · see citing works
Fibroblast growth factor 21 in lipid metabolism and non-alcoholic fatty liver disease
Su, X., Kong, Y., & Peng, D. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.08.005 · Cited by 40 · see citing works
Targeting Neurovascular Interaction in Retinal Disorders
Fu, Z., Sun, Y., Cakir, B., Tomita, Y., Huang, S., Wang, Z., Liu, C., Cho, S. S., Britton, W. R., Kern, T. S., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041503 · Cited by 41 · see citing works
Adipocyte function and the development of cardiometabolic disease
Giroud, M., Jodeleit, H., Prentice, K. J., & Bartelt, A. (2021) · The Journal of Physiology · doi:10.1113/jp281979 · Cited by 40 · see citing works
“2014b), while another well-studied endocrine factor reportedly released by BAT, FGF21, regulates nutrient disposal into adipose tissue (Schlein et al. 2016).”
BackgroundYamashita, S., Rizzo, M., Su, T., & Masuda, D. (2023) · Metabolites · doi:10.3390/metabo13050626 · Cited by 40 · see citing works
“FGF21 accelerates fatty acid β-oxidation and PPARα is known to regulate the expression of FGF21 [41,42], which decreases hepatic VLDL secretion by regulating fatty acids uptake by adipose tissue [43].”
BackgroundFGF21 and Chronic Kidney Disease.
Salgado, J., Goes, M. A., & Salgado, N. (2021) · Metabolism: Clinical and Experimental · doi:10.1016/j.metabol.2021.154738 · Cited by 35 · see citing works
Current and emerging therapeutic landscape for metabolic dysfunction-associated steatohepatitis
Li, W., Alazawi, W., & Loomba, R. S. (2025) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(25)00260-2 · Cited by 43 · see citing works
Libby, A. E., Bales, E. S., Monks, J., Orlicky, D. J., & McManaman, J. L. (2018) · Journal of Lipid Research · doi:10.1194/jlr.m086249 · Cited by 38 · see citing works
“Browning of WAT has been shown to have beneficial effects on adipocity, energy expenditure, serum lipid profiles, and glucose tolerance (17, 31).”
BackgroundSommakia, S., Almaw, N. H., Lee, S. H., Ramadurai, D. K. A., Taleb, I., Kyriakopoulos, C. P., Stubben, C., Jing, L., Campbell, R. A., Alharethi, R. A., et al. (2021) · Circulation Heart Failure · doi:10.1161/circheartfailure.121.008910 · Cited by 38 · 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
“Furthermore, FGF21 also promoted the catabolism of TG-rich lipoproteins in white adipose tissue and brown adipose tissue (100).”
BackgroundIs activation of human brown adipose tissue a viable target for weight management?
Marlatt, K. L., Chen, K. Y., & Ravussin, É. (2018) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00443.2017 · Cited by 36 · see citing works
“Despite the lack of human research to support the use of BAT activation to induce weight loss and combat obesity, there are noteworthy observations of improved glucose metabolism and insulin sensitivity in humans (6, 8, 10, 13, 17, 19–21, 24, 26, 31, 37, 38, 42, 43) as well as other cardioprotective effects, such as i…”
BackgroundJaved, K., & Bröer, S. (2019) · Nutrients · doi:10.3390/nu11092024 · Cited by 37 · see citing works
- Authors
- Schlein, C., Talukdar, S., Heine, M., Fischer, A. W., Krott, L. M., Nilsson, S. K., Brenner, M. B., Heeren, J., & Scheja, L.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Pfizer (United States) (US)
- Corresponding author
- Scheja, Ludger
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 23
- Issue
- 3
- Pages
- 441-453
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2253407701
- Cited by
- 252
- References
- 53
- Citations by year
- 2026: 18 · 2025: 18 · 2024: 27 · 2023: 20 · 2022: 26 · 2021: 27 · 2020: 30 · 2019: 33 · 2018: 19 · 2017: 21 · 2016: 11
- FWCI
- 14.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- FGF21, plasma triglycerides, triglyceride-rich lipoproteins, lipoprotein catabolism, white adipose tissue, brown adipose tissue, CD36, lipoprotein lipase, free fatty acids, hepatic lipid metabolism, insulin resistance, diet-induced obesity, ob/ob mice
- MeSH terms
- Animals, Hypolipidemic Agents, Adipose Tissue, Brown, Cells, Cultured, Drug Evaluation, Preclinical, Female, Fibroblast Growth Factors, Humans, Lipoproteins, VLDL, Liver, Male, Mice, Inbred C57BL, Triglycerides, Mice, Knockout, Hepatocytes, Lipid Metabolism, Adipose Tissue, White, Adipocytes, White
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