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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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MitoNEET in Perivascular Adipose Tissue Blunts Atherosclerosis under Mild Cold Condition in Mice
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“Additionally, WAT can be converted to “beige” fat (between WAT and BAT) by cold stimuli or hormones such as irisin (Zhang et al., 2014), FGF21 (Fisher et al., 2012), etc.”
Hepatic tristetraprolin promotes insulin resistance through RNA destabilization of FGF21
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“Additionally, FGF21 signaling leads to increased glucose uptake in skeletal muscle, as well as in beige AT and bAT (28, 36).”
BackgroundThe kallikrein–kinin pathway as a mechanism for auto-control of brown adipose tissue activity
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“For example, FGF21 is known to stimulate WAT browning (Fisher et al., 2012) and acute exercise has been shown to increase circulating FGF21 in both mice and humans (Kim et al., 2013).”
BackgroundAnatomy and physiology of the nutritional system
Cinti, S. (2019) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2019.04.001 · Cited by 37
p107 Is a Crucial Regulator for Determining the Adipocyte Lineage Fate Choices of Stem Cells
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Of mice and men: novel insights regarding constitutive and recruitable brown adipocytes
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“Several studies have demonstrated that continuous administration of FGF21 either for short or long durations increases UCP1 expression in the adipose tissue in mice [6, 41].”
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Chlorogenic acid promotes development of brown adipocyte-like phenotype in 3T3-L1 adipocytes
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Factors Associated with White Fat Browning: New Regulators of Lipid Metabolism
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“Fibroblast growth factor 21 (FGF21) regulates protein levels of PGC-1α at the post-transcriptional level and activates subcutaneous fat browning as well as thermogenesis of brown fat in mice [62].”
BackgroundThermogenic adipose tissue aging: Mechanisms and implications
Silva, G. D. N., & Amato, A. A. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.955612 · Cited by 39
“The latter effect is mediated activation of brown adipose tissue and recruitment and activation of beige adipocytes by direct actions on adipose tissue (Fisher et al., 2012) and central actions to increase sympathetic activity (Owen et al.”
BackgroundCircadian Dysfunction in Adipose Tissue: Chronotherapy in Metabolic Diseases
Civelek, E., Civelek, D. Ö., Akyel, Y. K., Durman, D. K., & Okyar, A. (2023) · Biology · doi:10.3390/biology12081077 · Cited by 35
“A midnight injection of bezafibrate significantly stimulated PPARα-dependent FGF21 expression, which is crucial for adaptations to fasting, including lipolysis and ketogenesis, but a daytime infusion had little impact.”
BackgroundInfluentialStone, K. P., Wanders, D., Calderon, L. F., Spurgin, S. B., Scherer, P. E., & Gettys, T. W. (2015) · Obesity · doi:10.1002/oby.21177 · Cited by 32
“FGF21 also acts directly on white adipocytes to induce browning (34) and enhance insulin-dependent glucose uptake (1).”
BackgroundGenetic backgrounds determine brown remodeling of white fat in rodents
Ferrannini, G., Namwanje, M., Fang, B., Damle, M., Li, D., Liu, Q., Lazar, M. A., & Qiang, L. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.08.013 · Cited by 33
van der Stelt, I., Hoevenaars, F. P. M., Široká, J., de Ronde, L., Friedecký, D., Keijer, J., & van Schothorst, E. M. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00179 · Cited by 32
“…of Fgf21, Ppargc1a, and Ucp1 in BAT showed a similar response as found previously in cold (4–10◦C) exposure experiments (Puigserver et al., 1998; Fisher et al., 2012; Shore et al., 2013; Ye et al., 2013), confirming that the relatively modest decrease in temperature from…”
BackgroundFujii, N., Uta, S., Kobayashi, M., Sato, T., Okita, N., & Higami, Y. (2019) · Experimental Gerontology · doi:10.1016/j.exger.2019.01.001 · Cited by 32
“Moreover, Fgf21 expression is upregulated by PPARγ and PPARγ coactivator-1α (PGC-1α) via feed-forward autocrine/paracrine loops (Dutchak et al., 2012; Fisher et al., 2012) in WAT.”
Post, A., Dam, W., Sokooti, S., Groothof, D., Gloerich, J., van Gool, A. J., Kremer, D., Gansevoort, R. T., van den Born, J., Kema, I. P., et al. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac729 · Cited by 30
Regulatory networks of non-coding RNAs in brown/beige adipogenesis
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The Ablation of Mitochondrial Protein Phosphatase Pgam5 Confers Resistance Against Metabolic Stress
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“, 2011) andultimately protectsmice fromcold (Fisher et al., 2012).”
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Nesfatin-1 promotes brown adipocyte phenotype
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“In WAT, FGF21 positively regulates PGC-1α and PPARγ expression and/or activity via feed-forward autocrine/paracrine loops [26,27].”
BackgroundEffect of Thyroid Hormones on Adipose Tissue Flexibility
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“It is expressed mostly in the liver, adipocytes and skeletal muscle, correlating positively with the increase in EE and thermogenesis activation, and therefore, promoting browning within the AT [56,75].”
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Brown and beige fat: the metabolic function, induction, and therapeutic potential
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β-Hydroxy-β-methylbutyrate modulates lipid metabolism in adipose tissues of growing pigs
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The “Skinny” on brown fat, obesity, and bone
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“Key browning factors include cardiac natriuretic peptides (Bordicchia Yearbook of Physical Anthropology et al., 2012), fibroblast growth factor-21 (FGF21) (Fisher et al., 2012), and the hormone irisin (Bostrom et al., 2012), all of which can induce browning in human as well as murine adipocytes in vitro (Bordicchia et…”
BackgroundInfluentialEffect of mitochondrial stress on systemic metabolism
Lee, M. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12822 · Cited by 32
The role of FGF21 in type 1 diabetes and its complications
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“In addition, a previous study found Nrf2-mediated upregulation of FGF21 in the liver, but not in other tissues, including WAT, BAT, and islets [107].”
BackgroundInfluentialXiang, A. S., Meikle, P. J., Carey, A. L., & Kingwell, B. A. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.07.002 · Cited by 29
“…response to cold, preclinical studies have revealed several endogenous molecules which may induce browning and present potential as therapeutic candidates (Fisher et al., 2012; Montanari, Poscic, & Colitti, 2017; Owen et al., 2014; Villarroya, Cereijo, et al., 2017). adipose tissue (BAT).”
BackgroundHirai, T., Mitani, Y., Kurumisawa, K., Nomura, K., Wang, W., Nakashima, K., & Inoue, M. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.04.017 · Cited by 31
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“FGF21-deficient mice exhibit decreased cold-induced thermogenic gene expression in WAT but not BAT (6).”
InfluentialAhuja, P., Bi, X., Ng, C. F., Tse, M. C. L., Hang, M., Pang, B. P. S., Iu, E. C. Y., Chan, W. S., Ooi, X. C., Sun, A., et al. (2022) · Hepatology · doi:10.1002/hep.32501 · Cited by 30
“Moreover, browning of gWAT was also observed in the mice with high hepatic SBK1 content, which we rationalize as a consequence of FGF21‐induced PPARa expression[28] in the tissue (Figure 5).”
BackgroundResultSrinivasa, S., Wong, K., Fitch, K. V., Wei, J., Petrow, E., Cypess, A. M., Torriani, M., & Grinspoon, S. K. (2014) · Clinical Endocrinology · doi:10.1111/cen.12582 · Cited by 30
Browning and Graying: Novel Transcriptional Regulators of Brown and Beige Fat Tissues and Aging
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“In addition to the classic inducers of brown fat function, such as β-adrenergic stimuli and CREB signaling, known to regulate PGC1α mRNAs, it has been demonstrated that PGC1α protein levels can be regulated in an autocrine/paracrine fashion by factors such as FGF21, prompting PGC1α-dependent browning of iWAT (21).”
BackgroundTFEB-dependent induction of thermogenesis by the hepatocyte SLC2A inhibitor trehalose
Zhang, Y., Higgins, C. B., Mayer, A. L., Mysorekar, I. U., Razani, B., Graham, M. J., Hruz, P. W., & DeBosch, B. J. (2018) · Autophagy · doi:10.1080/15548627.2018.1493044 · Cited by 30
Impact of adipokines and myokines on fat browning
Rodríguez, A., Catalán, V., Ramírez, B., Unamuno, X., Portincasa, P., Gómez‐Ambrosi, J., Frühbeck, G., & Becerril, S. (2020) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-020-00736-2 · Cited by 31
“FGF21 acts as a metabolic regulator, controlling glucose and lipid homeostasis [71], and ketogenesis, as well as energy expenditure and fat browning in both WAT and BAT [35, 63].”
BackgroundInfluentialCancer and Heterogeneity of Obesity: A Potential Contribution of Brown Fat
Berstein, L. M. (2012) · Future Oncology · doi:10.2217/fon.12.150 · Cited by 29
Biodegradable Polymeric Microsphere-Based Drug Delivery for Inductive Browning of Fat
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Singh, R., Pervin, S., Lee, S., Kuo, A., Grijalva, V. R., David, J., Vergnes, L., & Reddy, S. T. (2018) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s159315 · Cited by 29
Multifaceted Roles of Beige Fat in Energy Homeostasis Beyond UCP1
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“Recent work has demonstrated that FGF21 stimulates thermogenic gene expression BAT and induces iWAT browning (20,28-30).”
BackgroundAdipose‐specific ATGL ablation reduces burn injury‐induced metabolic derangements in mice
Kaur, S., Auger, C., Barayan, D., Shah, P., Matveev, A., Knuth, C. M., Harris, T. E., & Jeschke, M. G. (2021) · Clinical and Translational Medicine · doi:10.1002/ctm2.417 · Cited by 29
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“For example, MHB may contain direct activators of BAT thermogenesis, such as a β3-adrenergic agonist [38] and a TGR5 agonist [39], or affect the endocrine/paracrine activators, such as heart-derived natriuretic peptides (NP) [40] and fibroblast growth factor 21 (FGF21) [41].”
BackgroundMurphy, M., Samms, R. J., Warner, A., Bolborea, M., Barrett, P., Fowler, M. J., Brameld, J. M., Tsintzas, K., Kharitonenkov, A., Adams, A. C., et al. (2012) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2012.02383.x · Cited by 29
“…by Coskun et al. (19) and Hale et al. (13), who observed robust physiological responses to FGF21 in dietary-induced obese mice or leptin-deficient obese mice, but contrast with those of Fisher et al. (12), who observed attenuated intracellular responses to FGF21 in similar murine models of obesity.”
ResultAdenylyl Cyclase Type 5 Deficiency Protects Against Diet-Induced Obesity and Insulin Resistance
Ho, D., Zhao, X., Yan, L., Yuan, C., Zong, H., Vatner, D. E., Pessin, J. E., & Vatner, S. F. (2015) · Diabetes · doi:10.2337/db14-0494 · Cited by 28
“It was unexpected to find that the body temperature was similar in the AC5 WT and AC5KO mice, since in most cases animals with higher EE and more white fat browning have higher temperatures (26,27).”
ResultNelson, B. T., Ding, X., Bonéy-Montoya, J., Gerard, R. D., Kliewer, S. A., & Andrews, M. T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053574 · Cited by 28
Choi, M., Park, H., Kim, S. R., Kim, D. Y., & Jung, U. J. (2017) · Journal of Medicinal Food · doi:10.1089/jmf.2017.3995 · Cited by 32
Burke, S. J., Batdorf, H. M., Martin, T. M., Burk, D. H., Noland, R. C., Cooley, C. R., Karlstad, M. D., Johnson, W. D., & Collier, J. J. (2018) · Obesity · doi:10.1002/oby.22217 · Cited by 29
Biagioli, M., Carino, A., Fiorucci, C., Annunziato, G., Marchianò, S., Bordoni, M., Roselli, R., Giorgio, C. D., Castiglione, F., Ricci, P., et al. (2019) · Nutrients · doi:10.3390/nu11081820 · Cited by 30
“Because treatment of obese mice with FGF21 leads to weight loss and increased energ expe di ure through the activation of eWAT or BAT [51,52], it is likely that FGF-21 mRNA up-regulation n the liver might explain some of the beneficial effects exerted by Mt-P.”
BackgroundMin, B.-K., Oh, C. J., Park, S., Lee, J.-M., Go, Y., Park, B.-Y., Kang, H., Kim, D. W., Kim, J., Yoo, E. K., et al. (2019) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0315-2 · Cited by 28
AMPK in the Ventromedial Nucleus of the Hypothalamus: A Key Regulator for Thermogenesis
Liu, H., Xu, Y., & Hu, F. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.578830 · Cited by 30
Moure, R., Cairó, M., Morón‐Ros, S., Quesada‐López, T., Campderrós, L., Cereijo, R., Hernáez, Á., Villarroya, F., & Giralt, M. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00270.2020 · Cited by 28
Karampatsou, S., Genitsaridi, S. M., Michos, A. G., Kourkouni, Ε., Kourlaba, G., Kassari, P., Μanios, Y., & Charmandari, E. (2021) · Nutrients · doi:10.3390/nu13041274 · Cited by 28
“It regulates glucose and lipid metabolism [24,25], and activates thermogenesis in response to exposure to cold [23].”
BackgroundSex differences and aging: Is there a role of brown adipose tissue?
Hoffman, J. M., & Valencak, T. G. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111310 · Cited by 29
Annunziata, C., Pirozzi, C., Lama, A., Senzacqua, M., Comella, F., Bordin, A., Monnolo, A., Pelagalli, A., Ferrante, M. C., Mollica, M. P., et al. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14020338 · Cited by 30
“Moreover, PEA increased the expression of FGF21 (Figure 3F), an adipocyte secreted protein able to promote the browning effect mainly through the induction of PGC-1α [30].”
BackgroundMice lacking triglyceride synthesis enzymes in adipose tissue are resistant to diet-induced obesity
Chitraju, C., Fischer, A. W., Ambaw, Y. A., Wang, K., Yuan, B., Hui, S. T., Walther, T. C., & Farese, R. V. (2023) · eLife · doi:10.7554/elife.88049 · Cited by 36
White, brite, and brown adipocytes: the evolution and function of a heater organ in mammals
Li, Y., Lasar, D., Fromme, T., & Klingenspor, M. (2013) · Canadian Journal of Zoology · doi:10.1139/cjz-2013-0165 · Cited by 29
“Multiple studies have utilized CideA expression as a robust marker for the appearance of brite adipocytes in WAT (Madsen et al. 2010; Meyer et al. 2010; Vegiopoulos et al. 2010; Fisher et al. 2012; Lasar et al. 2013).”
BackgroundReduced adiposity by compensatory WAT browning upon iBAT removal in mice
Piao, Z., Zhai, B., Jiang, X., Dong, M., Yan, C., Lin, J., & Jin, W. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.05.089 · Cited by 28
Growth hormone activated STAT5 is required for induction of beige fat in vivo
Nelson, C. N., List, E. O., Ieremia, M., Constantin, L., Chhabra, Y., Kopchick, J. J., & Waters, M. J. (2018) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2018.08.004 · Cited by 26
Horváth, C., & Wolfrum, C. (2020) · Proceedings of The Nutrition Society · doi:10.1017/s0029665120006928 · Cited by 29
Adapting to the cold: A role for endogenous fibroblast growth factor 21 in thermoregulation?
Klein Hazebroek, M., & Keipert, S. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00389 · Cited by 27
“The pharmacological administration of native FGF21 in mouse and human studies induces thermogenic gene expression inWAT and BAT, for example,Ucp1 andDio2 (8, 9, 16).”
BackgroundDa, W., Chen, Q., & Shen, B. (2024) · Biological Research · doi:10.1186/s40659-024-00494-1 · Cited by 32
“The autocrine activity of FGF21 induces the upregulation of PGC-1α, enhancing mitochondrial oxidation function by activating AMPK and SIRT1 [72, 73].”
BackgroundUnger, R. H., Scherer, P. E., & Holland, W. L. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-10-0774 · Cited by 28
“The authors were supported by the National Institutes of Health (NIH; grant K99-DK094973) and an American Heart Association Beginning Grant-in-Aid (12BGI-A8910006) to W.L.H. and NIH grants (R01-DK55758 and P01-DK088761) to P.E.S.”
MethodA critical appraisal of brown adipose tissue metabolism in humans
Blondin, D. P., Labbé, S. M., Turcotte, É. E., Haman, F., Richard, D., & Carpentier, A. C. (2015) · Clinical Lipidology · doi:10.2217/clp.15.14 · Cited by 29
Hirai, T., Nomura, K., Ikai, R., Nakashima, K., & Inoue, M. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.10.154 · Cited by 28
Zhang, Y., Song, K., Qi, G., Yan, R., Yang, Y., Li, Y., Wang, S., Bai, Z., & Ge, R. (2020) · Scientific Reports · doi:10.1038/s41598-020-71345-8 · Cited by 27
Cheong, L. Y., & Xu, A. (2021) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjab038 · Cited by 28
“(Fisher et al., 2012; Huang et al., 2017) or even leads to a decrease in the level of circulating FGF21”
BackgroundInfluentialDi(2-ethylhexyl)phthalate exposure exacerbates metabolic disorders in diet-induced obese mice
Hsu, J.-W., Nien, C.-Y., Chen, H., Tsai, F., Yeh, S., Kao, Y.-H., & Tsou, T. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112439 · Cited by 29
Albumin-fused long-acting FGF21 analogue for the treatment of non-alcoholic fatty liver disease
Chikamatsu, M., Watanabe, H., Shintani, Y., Murata, R., Miyahisa, M., Nishinoiri, A., Imafuku, T., Takano, M., Arimura, N., Yamada, K., et al. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.01.039 · Cited by 27
Knuth, C. M., Peppler, W. T., Townsend, L. K., Miotto, P. M., Gudiksen, A., & Wright, D. C. (2018) · The Journal of Physiology · doi:10.1113/jp276228 · Cited by 27
“In an effort to address this question we measured serum creatine kinase activity, a marker of cold-induced shivering used by several other groups (Fisher et al. 2012; Tran et al. 2016).”
BackgroundMethodOpportunities and challenges in three-dimensional brown adipogenesis of stem cells
Unser, A. M., Tian, Y. I., & Xie, Y. (2015) · Biotechnology Advances · doi:10.1016/j.biotechadv.2015.07.005 · Cited by 29
“Additionally, certain adipocyte markers such as PGC1α, PRDM16, FGF21, and FOXC2 (Cederberg et al., 2001; Seale et al., 2007; Hondares et al. 2011; Fisher et al., 2012) are expressed at higher levels in brown than white adipocytes.”
BackgroundMicrofluidic systems for studying dynamic function of adipocytes and adipose tissue
Li, X., & Easley, C. J. (2017) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-017-0741-8 · Cited by 26
Xiao, F., Guo, Y., Deng, J., Yuan, F., Xiao, Y., Hui, L., Li, Y., Hu, Z., Zhou, Y., Li, K., et al. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.12.003 · Cited by 28
Maresin 1 Regulates Hepatic FGF21 in Diet‐Induced Obese Mice and in Cultured Hepatocytes
Martínez‐Fernández, L., González‐Muniesa, P., Sáinź, N., Laiglesia, L. M., Escoté, X., Martínez, J. A., & Moreno-Aliaga, M. J. (2019) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900358 · Cited by 26
GATA3 induces the upregulation of UCP-1 by directly binding to PGC-1α during adipose tissue browning
Son, M. J., Oh, K., Park, A., Kwon, M., Suh, J. M., Kim, I., Kim, S., Lee, S. C., Kim, W. K., & Bae, K. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154280 · Cited by 26
FGF21 impedes peripheral myelin development by stimulating p38 MAPK/c‐Jun axis
Zhang, Y., Jiang, K., Xie, G., Ding, J., Su, P., Liu, X., Sun, C., & Tang, X. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29942 · Cited by 24
“Among them, FGF21 receives much more attention due to its crucial roles in energy homeostasis regulation (Fisher & Maratos‐Flier, 2016; Fisher et al., 2012; Hondares et al., 2011; P. Lee et al., 2014; Vernia, Cavanagh‐Kyros, Barrett, Tournier, & Davis, 2016; Vernia et al., 2014).”
BackgroundMolecular pathways regulating the formation of brown‐like adipocytes in white adipose tissue
Fu, J., Li, Z., Zhang, H., Mao, Y., Wang, A., Wang, X., Zou, Z., & Zhang, X. (2014) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2600 · Cited by 29
“Even more interestingly, this process is associated with a large induction of PGC-1α protein in adipose tissue [157].”
BackgroundLi, E., Wang, T., Wang, F., Wang, T., Sun, L., Li, L., Niu, S., & Zhang, J. (2015) · BMC Cardiovascular Disorders · doi:10.1186/s12872-015-0077-2 · Cited by 26
“Moreover, CHOP is found to induce cell apoptosis through activating death receptor 5 (DR5) in human carcinoma cells [20].”
BackgroundBhat, M., Noolu, B., Qadri, S. S. Y. H., & Ismail, A. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.08.005 · Cited by 26
Lear, P., González-Touceda, D., Couto, B. P., Viaño, P., Guymer, V., Remzova, E., Tunn, R., Chalasani, A., García‐Caballero, T., Hargreaves, I. P., et al. (2014) · Endocrinology · doi:10.1210/en.2014-1766 · Cited by 26
Tanaka‐Yachi, R., Takahashi-Muto, C., Adachi, K., Tanimura, Y., Aoki, Y., Koike, T., & Kiyose, C. (2017) · Journal of Oleo Science · doi:10.5650/jos.ess16137 · Cited by 26
FGF21 regulates insulin sensitivity following long-term chronic stress
Jeleník, T., Dille, M. A., Müller-Lühlhoff, S., Kabra, D. G., Zhou, Z., Binsch, C., Hartwig, S., Lehr, S., Chadt, A., Peters, E. M. J., et al. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.06.012 · Cited by 26
Jena, J., García-Peña, L. M., Weatherford, E. T., Marti, A., Bjorkman, S. H., Kato, K. M., Koneru, J., Chen, J. H., Seeley, R. J., Abel, E. D., et al. (2023) · eLife · doi:10.7554/elife.86452 · Cited by 25
Beyond the Cold: Activating Brown Adipose Tissue as an Approach to Combat Obesity
Negroiu, C. E., Tudorașcu, I., Bezna, C. M., Godeanu, S., Diaconu, M., Dănoiu, R., & Dănoiu, S. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13071973 · Cited by 28
“It enhances the expression of thermogenic genes like UCP1 and DIO2 (stromal iodothyronine deiodinase 2), improving insulin sensitivity and having beneficial effects on body weight while lowering blood glucose and lipid levels [80,81].”
BackgroundActivation of hypothalamic RIP‐Cre neurons promotes beiging of WAT via sympathetic nervous system
Wang, B., Li, A., Li, X., Ho, P. W., Wu, D., Wang, X., Liu, Z., Wu, K. K.-L., Yau, S., Xu, A., et al. (2018) · EMBO Reports · doi:10.15252/embr.201744977 · Cited by 25
β-Klotho deficiency shifts the gut-liver bile acid axis and induces hepatic alterations in mice
Somm, E., Henry, H., Bruce, S. J., Bonnet, N., Montandon, S. A., Niederländer, N. J., Messina, A., Aeby, S., Rosikiewicz, M., Fajas, L., et al. (2018) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00182.2018 · Cited by 28
Identification of a rhodanine derivative BML-260 as a potent stimulator of UCP1 expression
Feng, Z., Wei, Y., Zhang, Y., Qiu, Y., Liu, X., Su, L., Liang, N., Yin, H., & Ding, Q. (2019) · Theranostics · doi:10.7150/thno.31951 · Cited by 25
“BAT, brown adipose tissue; BP, biological process; cAMP, 3’,5’cyclic adenosine monophosphate; CC, cellular component; CMAP, connectivity map; CL, CL-316243; DMSO, dimethyl sulfoxide; DUSP22, dual specificity phosphatase 22; FGF21, fibroblast growth factor 21; HPLC, high performance liquid chromatography; ISO, isoprote…”
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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