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FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis
Open accessAbstract
Certain white adipose tissue (WAT) depots are readily able to convert to a "brown-like" state with prolonged cold exposure or exposure to β-adrenergic compounds. This process is characterized by the appearance of pockets of uncoupling protein 1 (UCP1)-positive, multilocular adipocytes and serves to increase the thermogenic capacity of the organism. We show here that fibroblast growth factor 21 (FGF21) plays a physiologic role in this thermogenic recruitment of WATs. In fact, mice deficient in FGF21 display an impaired ability to adapt to chronic cold exposure, with diminished browning of WAT. Adipose-derived FGF21 acts in an autocrine/paracrine manner to increase expression of UCP1 and other thermogenic genes in fat tissues. FGF21 regulates this process, at least in part, by enhancing adipose tissue PGC-1α protein levels independently of mRNA expression. We conclude that FGF21 acts to activate and expand the thermogenic machinery in vivo to provide a robust defense against hypothermia.
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“and possibly mediates an hepatokine–myokine crosstalk via activation of PGC-1α [43]”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [43]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“have also been described to induce WAT browning directly (6).”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [43]
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In the citing paper
“In WAT, it induces lipolysis [166] and browning [43], likely via upregulation of PGC-1α [192].”
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In the citing paper
“the exercise-induced hepatokines FGF21 [43] and follistatin [185], both upregulated by glucagon (5)”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [43]
Experimental — accuracy not yet measuredIn the citing paper
“The direct effect of Fgf21 on adipocyte browning has also been demonstrated by others [284].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [284]
In the citing paper
“Consistent with a functional role for FGF21 during cold, both Fgf21 total knockout mice (36) and adipose-specific Fgf21 knockout mice (52) exhibit reduced body temperature in response to acute cold exposure.”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [36]
In the citing paper
“However, while an increase in circulating levels of FGF21 has been reported in response to cold in mice (49), this has not been observed in other studies (36, 52).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [36]
In the citing paper
“Fgf21 mRNA expression is upregulated in both WAT (36, 52) and BAT (15, 36, 49, 52) in response to cold.”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [36]
In the citing paper
“Consistent with its role in regulating thermogenesis, FGF21 treatment is sufficient to increase thermogenic gene expression in mouse primary white adipocytes (36).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [36]
In the citing paper
“Some teams have reported that FGF21 knockout mice have impaired adaptation to chronic cold exposure and decreased browning of WAT 92.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [92]
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Citations
Cites
1 retracted
Romanatto, T., Roman, E. A., Arruda, A. P., Denis, R., Solon, C., Milanski, M., Moraes, J. C., Bonfleur, M. L., Degasperi, G. R., Picardi, P. K., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.030874 · Cited by 156
RetractedWu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139
PRDM16 controls a brown fat/skeletal muscle switch
Seale, P., Bjork, B., Yang, W., Kajimura, S., Chin, S., Kuang, S., Scimè, A., Devarakonda, S., Conroe, H. M., Erdjument-Bromage, H., et al. (2008) · Nature · doi:10.1038/nature07182 · Cited by 2,347
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
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
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
Feldmann, H. M., Golozoubova, V., Cannon, B., & Nedergaard, J. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.12.014 · Cited by 1,318
Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice
Seale, P., Conroe, H. M., Estall, J. L., Kajimura, S., Frontini, A., Ishibashi, J., Cohen, P., Cinti, S., & Spiegelman, B. M. (2010) · Journal of Clinical Investigation · doi:10.1172/jci44271 · Cited by 1,273
Petrovic, N., Walden, T. B., Shabalina, I. G., Timmons, J. A., Cannon, B., & Nedergaard, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.053942 · Cited by 1,263
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
Cited by
Sorted by citations
Items 501–600 of 1,000
Neural Control of Energy Expenditure
Münzberg, H., Qualls‐Creekmore, E., Berthoud, H., Morrison, C. D., & Yu, S. (2015) · Handbook of experimental pharmacology · doi:10.1007/164_2015_33 · Cited by 53
“Incoming (afferent) sympathetic nerves can be distinguished from outgoing (efferent) sensory nerves with multisynaptic anterograde (Herpes virus) and retrograde (pseudorabies virus) viral tracers that are injected into BAT or WAT.”
InfluentialRush to the fire: FGF21 extinguishes metabolic stress, metaflammation and tissue damage
Luo, Y., Ye, S., Chen, X., Gong, F., Lu, W., & Li, X. (2017) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2017.08.001 · Cited by 56
Lee, C. S., Liu, M., Agha, O., Kim, H. T., Feeley, B. T., & Liu, X. (2019) · Journal of Orthopaedic Research® · doi:10.1002/jor.24558 · Cited by 55
“have demonstrated that brown adipocytes can promote white fat browning via BAT secretion of growth factors including fibroblast growth factor‐21 (FGF21) and vascular endothelial growth factor (VEGF).(27,28) Our study suggests that transplantation of beige FAPs significantly reduces FI in a massive RC tear model.”
BackgroundMicroRNAs in brown and beige fat
Goody, D., & Pfeifer, A. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2018.05.003 · Cited by 54
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
“It was reported that Fgf21 induced to express by cold exposure or rosiglitazone regulated Pparc activity in the white adipose tissue in an autocrine/paracrine manner, respectively, although it did not affect blood Fgf21 levels [24,25].”
BackgroundImran, K. M., Rahman, N., Yoon, D., Jeon, M., Lee, B., & Kim, Y. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2017.08.001 · Cited by 54
Circulating α-klotho regulates metabolism via distinct central and peripheral mechanisms
Landry, T., Shookster, D., & Hu, H. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154819 · Cited by 55
Recent advance in brown adipose physiology and its therapeutic potential
Lee, Y., Jung, Y.-S., & Choi, D. (2014) · Experimental & Molecular Medicine · doi:10.1038/emm.2013.163 · Cited by 56
Browning of White Adipose Tissue Uncouples Glucose Uptake from Insulin Signaling
Mössenböck, K., Vegiopoulos, A., Rose, A. J., Sijmonsma, T., Herzig, S., & Schafmeier, T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110428 · Cited by 57
miR-21 mimic blocks obesity in mice: A novel therapeutic option
Lhamyani, S., Gentile, A., Giráldez‐Pérez, R. M., Feijoo‐Cuaresma, M., Romero‐Zerbo, S., Clemente‐Postigo, M., Zayed, H., Oliva‐Olivera, W., Bermúdez‐Silva, F. J., Salas, J., et al. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.06.019 · Cited by 55
“Surprisingly, in adipocytes, the miR-21 mimic appears to significantly reduce the expression levels of both Cebp-a and Ppar-g, which are the master transcriptional regulators of adipogenesis,(45) whereas increasing the expression of Pgc-1a and Fgf21, genes well known to play a relevant role in BAT thermogenesis and WA…”
BackgroundResultRoberts, F. L., & Markby, G. R. (2021) · Cells · doi:10.3390/cells10102639 · Cited by 54
Merlin, J., Evans, B. A., Dehvari, N., Sato, M., Bengtsson, T., & Hutchinson, D. S. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500251 · Cited by 56
“Importantly, treatment of mice with CGS21680 for 10 days caused substantial increases in PGC-1 and UCP1 mRNA, and the appearance of small, multilocular brite adipocytes expressing UCP1 protein in iWAT depots [81].”
BackgroundInfluentialFunctional crosstalk of PGC-1 coactivators and inflammation in skeletal muscle pathophysiology
Eisele, P. S., & Handschin, C. (2013) · Seminars in Immunopathology · doi:10.1007/s00281-013-0406-4 · Cited by 54
Qiu, Y., Sun, Y., Xu, D., Yang, Y., Liu, X., Wei, Y., Chen, Y., Feng, Z., Li, S., Reyad‐ul‐Ferdous, M., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.10.019 · Cited by 53
Song, W., Luo, Q., Zhang, Y., Zhou, L., Liu, Y., Ma, Z., Guo, J., Huang, Y., Cheng, L., Meng, Z., et al. (2019) · PLoS Biology · doi:10.1371/journal.pbio.2006571 · Cited by 53
Ozaki, Y., Saito, K., Nakazawa, K., Konishi, M., Itoh, N., Hakuno, F., Takahashi, S.-I., Kato, H., & Takenaka, A. (2015) · British Journal Of Nutrition · doi:10.1017/s0007114515002846 · Cited by 51
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 60
“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).”
BackgroundChen, Y., Li, Q., Zhao, S., Sun, L., Yin, Z., Wang, X., Li, X., Iwakiri, Y., Han, J., & Duan, Y. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115928 · Cited by 55
FGF21 protects against HFpEF by improving cardiac mitochondrial bioenergetics in mice
Zhang, K., Gan, J., Wang, B., Lei, W., Dong, Z., Yang, J., Wang, N., Wen, C., Gao, X., Li, X., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56885-9 · Cited by 57
Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice
Grefhorst, A., van den Beukel, J. C., van Houten, E. L. A. F., Steenbergen, J., Visser, J. A., & Themmen, A. P. N. (2015) · Biology of Sex Differences · doi:10.1186/s13293-015-0025-y · Cited by 54
“FGF21 is secreted by activated BAT [21,22], and both FGF1 and FGF2 have been shown to upregulate UCP1 expression in cultured rat brown adipocytes [23].”
BackgroundJin, L., Lin, Z., & Xu, A. (2016) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2016.40.1.22 · Cited by 52
Hashidume, T., Kato, A., Tanaka, T., Miyoshi, S., Itoh, N., Nakata, R., Inoue, H., Oikawa, A., Nakai, Y., Shimizu, M., et al. (2016) · Scientific Reports · doi:10.1038/srep28183 · Cited by 52
Lv, Y., Zhang, S., Liang, X., Zhang, H., Zhi, X., Liu, B., Xu, M., Jiang, C., Shang, J., & Wang, X. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.735563 · Cited by 53
Cantó, C., & Auwerx, J. H. (2012) · Science · doi:10.1126/science.1222646 · Cited by 52
In vitro brown and “brite”/“beige” adipogenesis: Human cellular models and molecular aspects
Béranger, G. E., Karbiener, M., Barquissau, V., Pisani, D. F., Scheideler, M., Langin, D., & Amri, E. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.11.001 · Cited by 56
Martin, A., Ecklu-Mensah, G., Ha, C. W. Y., Hendrick, G., Layman, D. K., Gilbert, J. A., & Devkota, S. (2021) · Nature Communications · doi:10.1038/s41467-021-24074-z · Cited by 52
Brown Fat as a Regulator of Systemic Metabolism beyond Thermogenesis
Okamatsu‐Ogura, Y., & Saito, M. (2021) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2020.0291 · Cited by 55
“In contrast, FGF21 induces beige adipocyte biogenesis [74], suggesting that the FGF21 action is to stimulate some UCP1-independent mechanisms in beige adipocytes.”
BackgroundGliniak, 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
Ma, P.-Y., Li, X., Wang, Y., Lang, D.-Q., Liu, L., Yi, Y., Liu, Q., & Shen, C. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106175 · Cited by 52
Hypothalamic Estrogen Signaling and Adipose Tissue Metabolism in Energy Homeostasis
Irizarry, V. C. T., Jiang, Y., He, Y., & Xu, P. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.898139 · Cited by 54
Acupuncture promotes white adipose tissue browning by inducing UCP1 expression on DIO mice
Shen, W., Wang, Y., Lu, S.-F., Hong, H., Fu, S.-P., He, S.-Y., Li, Q., Yue, J., Xu, B., & Zhu, B. (2014) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-14-501 · Cited by 50
“Browning of WAT can be brought about by hormones, cytokines, and transcriptional modulation [21-23].”
BackgroundNot all fats are created equal: adipose vs. ectopic fat, implication in cardiometabolic diseases
Gaggini, M., Saponaro, C., & Gastaldelli, A. (2015) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2015-0006 · Cited by 51
Exercise training does not increase muscle FNDC5 protein or mRNA expression in pigs
Fain, J. N., Booth, F. W., Laughlin, M. H., Padilla, J., Jenkins, N. T., Bahouth, S. W., & Sacks, H. S. (2013) · Metabolism · doi:10.1016/j.metabol.2013.05.021 · Cited by 50
“FGF 21 was also examined because it has been reported to alter expression of thermogenic genes in fat tissue [12].”
BackgroundPeng, X., Gennemark, P., O’Mahony, G., & Bartesaghi, S. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00174 · Cited by 49
“Adiposederived FGF21 acts in an autocrine/paracrine manner to increase expression of UCP1 and other thermogenic genes, such as PGC1α, PRDM16, BMP8b, and DIO2 in iBAT and iWAT (134, 135).”
BackgroundThe regulation of FGF21 gene expression by metabolic factors and nutrients
Erickson, A., & Moreau, R. F. (2016) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2016-0016 · Cited by 53
Zhang, J., Xu, Z., Gu, J., Jiang, S., Liu, Q., Zheng, Y., Freedman, J. H., Sun, J., & Cai, L. (2018) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00465.2017 · Cited by 50
Apple polyphenols induce browning of white adipose tissue
Tamura, Y., Tomiya, S., Takegaki, J., Kouzaki, K., Tsutaki, A., & Nakazato, K. (2019) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2019.108299 · Cited by 51
Regulation of Energy Metabolism by Receptor Tyrosine Kinase Ligands
Zhao, M., Jung, Y., Jiang, Z., & Svensson, K. J. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00354 · Cited by 55
“FGF21 inhibits food intake through central effects (Kharitonenkov et al., 2005; Coskun et al., 2008; Xu et al., 2009; Ge et al., 2011; Fisher et al., 2012; Bookout et al., 2013; Minard et al., 2016; BonDurant et al., 2017).”
BackgroundSarcopenia and cachexia: molecular mechanisms and therapeutic interventions
Wang, T., Zhou, D., & Hong, Z. (2025) · MedComm · doi:10.1002/mco2.70030 · Cited by 46
McNeill, B. T., Suchacki, K. J., & Stimson, R. H. (2021) · European Journal of Endocrinology · doi:10.1530/eje-20-1439 · Cited by 55
“For example, fibroblast growth factor-21 (FGF21) release is induced by cold and increases UCP1 expression in murine WAT and BAT, and in human adipocytes (121, 122, 123).”
Adipose tissue plasticity and the pleiotropic roles of BMP signaling
Qian, S., Tang, Y., & Tang, Q. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100678 · Cited by 56
Multi-organ FGF21-FGFR1 signaling in metabolic health and disease
Kaur, N., Gare, S. R., Shen, J., Raja, R., Fonseka, O., & Liu, W. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.962561 · Cited by 49
“BAT-derived FGF21 either functions locally or escapes into the systemic circulation, having an autocrine as well as an endocrine role in thermogenesis via PGC-1α, mitogen-activated protein kinase (MAPK) and ERK signaling (27, 28, 36).”
BackgroundAutophagy as a crosstalk mediator of metabolic organs in regulation of energy metabolism
Kim, K. H., & Lee, M. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9272-6 · Cited by 50
MicroRNAs in dysfunctional adipose tissue: cardiovascular implications
Icli, B., & Feinberg, M. W. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx098 · Cited by 50
FGF21 induced by carbon monoxide mediates metabolic homeostasis via the PERK/ATF4 pathway
Joe, Y., Kim, S., Kim, H. J., Park, J., Chen, Y., Park, H.-J., Jekal, S., Ryter, S. W., Kim, U., & Chung, H. (2018) · The FASEB Journal · doi:10.1096/fj.201700709rr · Cited by 49
Zhuo, Y., Hua, L., Feng, B., Jiang, X., Li, J., Jiang, D., Huang, X., Yingguo, Z., Li, Z., Yan, L., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.02.020 · Cited by 49
White and brown adipose stem cells: From signaling to clinical implications
Algire, C., Medříková, D., & Herzig, S. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.10.001 · Cited by 48
“changes in mRNA, and positively affects the recruitment of adipocytes with thermogenic capabilities within WAT depots [72].”
BackgroundAhmadi, N., Nabavi, V., Hajsadeghi, F., Zeb, I., Flores, F. R., Ebrahimi, R., & Budoff, M. J. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.01.182 · Cited by 47
Bernardo, B. L., Lu, M. M., Bandyopadhyay, G. K., Li, P., Zhou, Y., Huang, J. S., Levin, N., Tomás, E., Calle, R. A., Erion, D. M., et al. (2015) · Scientific Reports · doi:10.1038/srep11382 · Cited by 49
Fgf21 is required for cardiac remodeling in pregnancy
Redondo‐Angulo, I., Mas‐Stachurska, A., Sitges, M., Tinahones, F. J., Giralt, M., Villarroya, F., & Planavila, A. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx088 · Cited by 48
“The endocrine actions of Fgf21 include: promoting glucose uptake by white adipocytes via induction of the glucose transporter, Glut1(9); activating brown fat thermogenic activity(10); and promoting the appearance of brown fat-like cells in white fat (the so-called “browning” process).(11) Fgf21 also has autocrine/para…”
BackgroundNeuronal growth regulator 1-deficient mice show increased adiposity and decreased muscle mass
Joo, Y., Kim, H., Lee, S.-J., & Lee, S. (2019) · International Journal of Obesity · doi:10.1038/s41366-019-0376-2 · Cited by 50
Crosstalk between CYP2E1 and PPARα substrates and agonists modulate adipose browning and obesity
Zhang, Y.-B., Yan, T., Wang, T., Liu, X., Hamada, K., Sun, D., Sun, Y., Yang, Y., Wang, J., Takahashi, S., et al. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.02.004 · Cited by 49
Xu, H., Lyu, X., Guo, X., Yang, H., Duan, L., Zhu, H., Pan, H., Gong, F., & Wang, L. (2022) · Nutrients · doi:10.3390/nu14091898 · Cited by 47
“Besides adipokines that are secreted primarily in adipose tissue, fibroblast growth factor 21 (FGF21) [12,13] and zinc-α2glycoprotein (ZAG) [14] were also reported to positively serve the whole-body metabolism targeting liver, eWAT, and other tissues.”
BackgroundXu, L., Li, D., Li, H., Zhang, O., Huang, Y., Shao, H., Wang, Y., Cai, S., Zhu, Y., Jin, S., et al. (2022) · Nutrition and Diabetes · doi:10.1038/s41387-022-00222-2 · Cited by 47
FGF-based drug discovery: advances and challenges
Chen, G., Chen, L., Li, X., & Mohammadi, M. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01125-w · Cited by 51
Glutathione Decrement Drives Thermogenic Program In Adipose Cells
Lettieri‐Barbato, D., Tatulli, G., Cannata, S. M., Bernardini, S., Aquilano, K., & Ciriolo, M. R. (2015) · Scientific Reports · doi:10.1038/srep13091 · Cited by 47
Verdeguer, F., Soustek, M. S., Hatting, M., Blättler, S. M., McDonald, D., Barrow, J. J., & Puigserver, P. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00722-15 · Cited by 47
Browning attenuates murine white adipose tissue expansion during postnatal development
Lasar, D., Grolleau‐Julius, A., Fromme, T., & Klingenspor, M. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.01.016 · Cited by 48
Bone and fat: A relationship of different shades
Lecka‐Czernik, B., & Stechschulte, L. A. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.06.010 · Cited by 48
Hydrodynamic delivery of FGF21 gene alleviates obesity and fatty liver in mice fed a high-fat diet
Gao, M., Ma, Y., Cui, R., & Liu, D. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.03.047 · Cited by 48
Symonds, M. E., Pope, M., & Budge, H. (2012) · Proceedings of The Nutrition Society · doi:10.1017/s0029665112000584 · Cited by 49
Diet-induced changes in Ucp1 expression in bovine adipose tissues
Asano, H., Yamada, T., Hashimoto, O., Umemoto, T., Sato, R., Ohwatari, S., Kanamori, Y., Terachi, T., Funaba, M., & Matsui, T. (2013) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2013.01.006 · Cited by 49
Chen, L., Chien, Y., Liang, C.-T., Chan, C., Fan, M., & Huang, H. (2017) · Food & Nutrition Research · doi:10.1080/16546628.2017.1347480 · Cited by 48
Liu, L., Zhou, M., Lang, H., Zhou, Y. G., & Mi, M. (2017) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13403 · Cited by 48
Agnew, T., Goldsworthy, M. E., Aguilar, C., Morgan, A., Simon, M., Hilton, H., Esapa, C. T., Wu, Y., Cater, H. L., Bentley, L., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.080 · Cited by 46
Dumesic, P. A., Egan, D. F., Gut, P., Tran, M. T., Parisi, A., Chatterjee, N., Jedrychowski, M. P., Paschini, M., Kazak, L., Wilensky, S. E., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.04.013 · Cited by 49
“Furthermore, discrepancies have been noted between the amount of mRNA and the corresponding PGC1a protein (Fisher et al., 2012; Pettersson-Klein et al., 2018; Tsukiyama-Kohara et al., 2001).”
BackgroundKim, O. Y., Chung, J. Y., & Song, J. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104411 · Cited by 48
Li, Z., Zhang, Z., Ke, L., Sun, Y., Li, W., Feng, X., Zhu, W., & Chen, S. (2020) · The FASEB Journal · doi:10.1096/fj.201902222r · Cited by 47
Schiffer, T. A., Lundberg, J. O., Weitzberg, E., & Carlström, M. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165811 · Cited by 49
(2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.07.012 · Cited by 46
Intermittent Cold Exposure Enhances Fat Accumulation in Mice
Yoo, H. S., Qiao, L., Bosco, C., Leong, L.-H., Lytle, N. K., Feng, G., Chi, N., & Shao, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096432 · Cited by 46
Loss of Adipose Fatty Acid Oxidation Does Not Potentiate Obesity at Thermoneutrality
Lee, J., Choi, J., Aja, S. M., Scafidi, S., & Wolfgang, M. J. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.01.029 · Cited by 46
“In support of this notion, fibroblast growth factor-21 has a strong effect on BAT but can increase energy expenditure and induce weight loss equally well in WT or Ucp1KO mice even at thermoneutrality (Fisher et al., 2012; Samms et al., 2015; Véniant et al., 2015).”
BackgroundLeng, Y., Wang, J., Wang, Z., Liao, H., Wei, M. H., Leeds, P. R., & Chuang, D. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw035 · Cited by 46
Sandoval, V., Femenias, A., Martínez‐Garza, Ú., Sanz‐Lamora, H., Castagnini, J. M., Quifer‐Rada, P., Lamuela-Raventós, R. M., Marrero, P. F., Haro, D., & Relat, J. (2019) · Antioxidants · doi:10.3390/antiox8090360 · Cited by 46
Man, A. W. C., Xia, N., & Li, H. (2020) · Antioxidants · doi:10.3390/antiox9100968 · Cited by 49
“Obesity-induced adipocyte hypertrophy is associated with reduced insulin sensitivity, increased oxidative stress, and abnormal adipokine secretory profile, including an elevated array of other pro-inflammatory factors [IL-1β, IL-8, resistin and monocyte chemoattractant protein 1 (MCP1)] and a reduced array of anti-inf…”
BackgroundInfluentialHepatic FGF21 preserves thermoregulation and cardiovascular function during bacterial inflammation
Huen, S. C., Wang, A., Feola, K. C., Desrouleaux, R., Luan, H. H., Hogg, R. T., Zhang, C., Zhang, Q.-J., Liu, Z., & Medzhitov, R. M. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20202151 · Cited by 46
“FGF21 is known to promote thermogenesis in cold adaptation (Fisher et al., 2012; Ameka et al., 2019) and increase energy expenditure (Owen et al.”
BackgroundMetabolic actions of fibroblast growth factor 21
Ramos, D. C., Aguilar-Salinas, C. A., & Gomez-Perez, F. J. (2012) · Current Opinion in Pediatrics · doi:10.1097/mop.0b013e3283557d22 · Cited by 46
Brown Fat-Derived Exosomes: Small Vesicles with Big Impact
Chen, Y., & Pfeifer, A. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.012 · Cited by 44
“Among other functions, FGF21 has been demonstrated to directly stimulate thermogenic capacity of BAT and to induce ‘‘browning’’ of WAT (Fisher et al., 2012).”
BackgroundCastro, É., Silva, T. E. O., & Festuccia, W. T. (2017) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2017-0042 · Cited by 48
“Physiological Cold SNS/catecholamine [18] Exercise FNDC5/irisin? [19] Disease/trauma Burn Catecholamine [20], [21] Cancer cachexia IL-6/PTHrP [22], [23] Pheochromocytoma Catecholamine [24] Endogenous/endocrine Adenosine A2A receptors [25] Adiponectin M2 macrophage/catecholamine [26] Cardiac natriuretic peptides NPR-PK…”
BackgroundPerivascular Adipose Tissue as a Target for Antioxidant Therapy for Cardiovascular Complications
Man, A. W. C., Zhou, Y., Xia, N., & Li, H. (2020) · Antioxidants · doi:10.3390/antiox9070574 · Cited by 45
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
Looking on the “brite” side exercise-induced browning of white adipose tissue
Townsend, L. K., & Wright, D. C. (2019) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2177-1 · Cited by 44
Fibroblast growth factor 21 in heart failure
Tucker, W., Tucker, B., Rye, K., & Ong, K. L. (2022) · Heart Failure Reviews · doi:10.1007/s10741-022-10268-0 · Cited by 44
Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases
Paluvai, H., Shanmukha, K. D., Tyedmers, J., & Backs, J. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1190094 · Cited by 48
“In response to specific environmental cues (such as exposure to cold), WAT shifts to a brown-like phenotype in a process known as browning (Fisher et al., 2012; Ohno et al., 2012).”
BackgroundMHO or MUO? White adipose tissue remodeling
Zhao, J. Y., Li, Z., Ma, K. L., Hao, R., & Li, M. (2024) · Obesity Reviews · doi:10.1111/obr.13691 · Cited by 49
Hinoi, E., Iezaki, T., Fujita, H., Watanabe, T., Odaka, Y., Ozaki, K., & Yoneda, Y. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.05.108 · Cited by 45
“These include b-adrenergic agonists [19], peroxisome proliferator-activated receptor-c agonists [20], prostaglandin [21] and fibroblast growth factor-21 [22].”
BackgroundThermogenic adipocytes: From cells to physiology and medicine
Díaz, M. B., Herzig, S., & Vegiopoulos, A. (2014) · Metabolism · doi:10.1016/j.metabol.2014.07.002 · Cited by 45
Hepatic insulin resistance and increased hepatic glucose production in mice lacking Fgf21
Camporez, J. P., Asrih, M., Zhang, D., Kahn, M., Samuel, V. T., Jurczak, M. J., & Jornayvaz, F. R. (2015) · Journal of Endocrinology · doi:10.1530/joe-15-0136 · Cited by 44
“1D), corroborating the role of FGF21 in inducing UCP1 gene expression in brown adipose tissue (Fisher et al. 2012).”
BackgroundNakagawa, Y., Oikawa, F., Mizuno, S., Ohno, H., Yagishita, Y., Satoh, A., Osaki, Y., Takei, K., Kikuchi, T., Han, S., et al. (2016) · Scientific Reports · doi:10.1038/srep27857 · Cited by 44
Weiner, J., Rohde, K., Krause, K., Zieger, K., Klöting, N., Kralisch, S., Kovacs, P. L., Stümvoll, M., Blüher, M., Böttcher, Y., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.03.004 · Cited by 44
Perilipin 3 Deficiency Stimulates Thermogenic Beige Adipocytes Through PPARα Activation
Lee, Y. K., Sohn, J. H., Han, J. S., Park, Y. J., Jeon, Y. G., Ji, Y., Dalen, K. T., Sztalryd, C., Kimmel, A. R., & Kim, J. B. (2018) · Diabetes · doi:10.2337/db17-0983 · Cited by 46
“Plin3 Deficiency Results in Elevated FGF21 Expression As FGF21 contributes to stimulation of beige adipocyte differentiation (33,34), we decided to test whether FGF21 might be associated with increased beige adipocytes in Plin3 KO mice.”
BackgroundWatanabe, M., Singhal, G., Fisher, F. M., Beck, T. C., Morgan, D. A., Socciarelli, F., Mather, M. L., Risi, R., Bourke, J., Rahmouni, K., et al. (2019) · Endocrine · doi:10.1007/s12020-019-02124-3 · Cited by 44
Hua, L., Feng, B., Huang, L., Li, J., Luo, T. F., Jiang, X., Han, X., Che, L., Xu, S., Lin, Y., et al. (2020) · Clinical and Translational Medicine · doi:10.1002/ctm2.195 · Cited by 43
A feed-forward regulatory loop in adipose tissue promotes signaling by the hepatokine FGF21
Han, M. S., Perry, R. J., Camporez, J.-P., Scherer, P. E., Shulman, G. I., Gao, G., & Davis, R. J. (2021) · Genes & Development · doi:10.1101/gad.344556.120 · Cited by 43
“These autocrine actions of FGF21 may be mediated, in part, by increased expression of the coactivator PGC1α and the expression of thermogenic genes (Fisher et al. 2012), increased PPARγ activity and insulin sensitization (Dutchak et al.”
BackgroundInfluentialLu, S., & Cao, Z. (2023) · Nutrients · doi:10.3390/nu15224832 · Cited by 46
“Serum VD levels show a negative correlation with VAT content and serve as an important indicator for assessing the expression of the VDR within VAT [74,82,83].”
BackgroundThe secretory function of adipose tissues in metabolic regulation
Liu, Y., Qian, S., Tang, Y., & Tang, Q. (2024) · Life Metabolism · doi:10.1093/lifemeta/loae003 · Cited by 53
The physiology of MASLD: molecular pathways between liver and adipose tissues
Lee, W., Kipp, Z. A., Bates, E. A., Pauss, S. N., Martinez, G. J., & Hinds, T. D. (2025) · Clinical Science · doi:10.1042/cs20257571 · Cited by 52
“FGF21 also stimulates the expression of uncoupling protein 1 (UCP1) and PGC-1α in adipose tissue, resulting in thermogenic and fat-burning effects [72].”
RGC32 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice
Cui, X., Luan, J.-N., Ye, J., & Chen, S. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0548 · Cited by 43
“PGC1a andUCP1 are highly expressed in brown adipose tissue (Fisher et al. 2012), and PRDM16 is a brown adipose determination factor (Seale et al.”
Breaking BAT: can browning create a better white?
Warner, A., & Mittag, J. (2015) · Journal of Endocrinology · doi:10.1530/joe-15-0408 · Cited by 45
Bravo, R., Mattar, P., Díaz, X., Lavandero, S., & Cifuentes, M. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00395 · Cited by 44
“White-to-brown transdifferentiation, commonly termed “browning” or “beigeing,” has been shown to occur only in subcutaneous (Fisher et al., 2012) but not in visceral WAT, further underscoring the differences between both types of adipose tissue and the need to explore the role of CaSR in the…”
Background
Metadata
- Authors
- 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., & Spiegelman, B. M.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- Eli Lilly (United States) (US)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-02-01
- Volume
- 26
- Issue
- 3
- Pages
- 271-281
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3278894
- OpenAlex
- W2145142659
- Cited by
- 1,478
- References
- 38
- Citations by year
- 2026: 44 · 2025: 58 · 2024: 90 · 2023: 82 · 2022: 100 · 2021: 122 · 2020: 112 · 2019: 121 · 2018: 128 · 2017: 126 · 2016: 131 · 2015: 127 · 2014: 101 · 2013: 94 · 2012: 40
- Type
- posted content
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DK028082, DK31405)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK028082, R01DK031405, DK-31405, R01DK028082, R37DK028082, R37DK031405)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- FGF21, PGC-1α, white adipose tissue browning, adaptive thermogenesis, UCP1, cold exposure, thermogenic gene expression, autocrine and paracrine signaling
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adaptation, Physiological, Animals, Adipose Tissue, Brown, Cell Differentiation, Cells, Cultured, Cold Temperature, Fibroblast Growth Factors, Gene Expression Regulation, Male, Mice, Inbred C57BL, RNA Processing, Post-Transcriptional, Transcription Factors, Trans-Activators, Thermogenesis, Mice, Adipose Tissue, White
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