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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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In the citing paper
“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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Items 201–300 of 1,000
Regulation of myokine expression: Role of exercise and cellular stress
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“Another mechanistic study demonstrated that FGF21 regulates this process, at least in part, by enhancing adipose tissue PGC-1 protein levels independent of mRNA expression (70).”
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“These data agree with the prior finding that FGF21 causes browning of white adipose tissue (30).”
ResultLSD1 promotes oxidative metabolism of white adipose tissue
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Inducible Brown Adipose Tissue, or Beige Fat, Is Anabolic for the Skeleton
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“…of Cpt2L / mice did not exhibit transcriptional increases in thermogenic genes (Figure 4F), but fasting elicited increases in Ucp1, Cidea, and Fgf21 in inguinal WAT (iWAT) of Cpt2L / mice (Figure 4G) consistent with fasting-induced Fgf21 target gene expression in this tissue (Fisher et al., 2012).”
Cold-induced lipid dynamics and transcriptional programs in white adipose tissue
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Apelin Enhances Brown Adipogenesis and Browning of White Adipocytes
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Bmp4 Promotes a Brown to White-like Adipocyte Shift
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PGC-1α affects skeletal muscle and adipose tissue development by regulating mitochondrial biogenesis
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FGF21 and Cardiac Physiopathology
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“Endocrine actions of FGF21 include the promotion of glucose uptake by white adipocytes through induction of the glucose transporter, Glut1 (7), activation of brown fat thermogenic activity (8), and promotion of the appearance of brown fat-like cells in white fat – the so-called “browning” process (9).”
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FGF21 mediates the lipid metabolism response to amino acid starvation
De Sousa-Coelho, A. L., Relat, J., Hondares, E., Pérez-Martí, A., Ribas, F., Villarroya, F., Marrero, P. F., & Haro, D. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m033415 · Cited by 123
Adipose Tissue Remodeling in Pathophysiology
Auger, C., & Kajimura, S. (2022) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-042220-023633 · Cited by 135
Long-Term Cold Adaptation Does Not Require FGF21 or UCP1
Keipert, S., Kutschke, M., Ost, M., Schwarzmayr, T., van Schothorst, E. M., Lamp, D., Brachthäuser, L., Hamp, I., Mazibuko, S. E., Hartwig, S., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.016 · Cited by 122
“Unexpectedly, the lack of FGF21 does not lead to any difference in energy metabolism and adipose thermogenic gene regulation during cold acclimation, in contrast to earlier statements (Fisher et al., 2012).”
BackgroundResultInfluentialHuang, 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
“FGF21 has also been shown to promote browning of white adipose tissues through regulating PPARg coactivator-1a (PGC-1a) (Fisher et al., 2012) and promote thermogenic activation in neonatal brown fat and primary brown adipocytes (Hondares et al., 2010).”
BackgroundFibroblast growth factor 21: a regulator of metabolic disease and health span
Xie, T., & Leung, P. S. (2017) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00101.2017 · Cited by 121
Regulation of longevity by FGF21: interaction between energy metabolism and stress responses
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“Finally, emerging evidence suggests that white adipose tissue has the capacity to “brown” and increase energy utilization [89–92], a process that may improve energy metabolism; whether and by which mechanisms EDCs affect this process remains largely unresolved.”
BackgroundThe Role of GDF15 as a Myomitokine
Johann, K., Kleinert, M., & Klaus, S. (2021) · Cells · doi:10.3390/cells10112990 · Cited by 125
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“In addition to its regulation of oxidative metabolism, Pgc1 regulates thermogenesis (44).”
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Evaluation of markers of beige adipocytes in white adipose tissue of the mouse
Garcia, R. A. G., Roemmich, J. N., & Claycombe, K. (2016) · Nutrition & Metabolism · doi:10.1186/s12986-016-0081-2 · Cited by 118
“FGF21 is a factor that induces beige cell differentiation in white adipose tissue, and its upregulation in the tissue may stimulate beige adipocyte differentiation through autocrine or paracrine effects [19].”
BackgroundmTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes
Minard, A. Y., Tan, S., Yang, P., Fazakerley, D. J., Domanova, W., Parker, B. L., Humphrey, S. J., Jothi, R., Stöckli, J., & James, D. E. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.08.086 · Cited by 122
“In adipocytes, FGF21 stimulates browning, adiponectin secretion, and glucose uptake (Fisher et al., 2012; Holland et al., 2013; Lin et al., 2013), and these effects are thought to underpin the beneficial effects of FGF21.”
BackgroundFGF21 activates AMPK signaling: impact on metabolic regulation and the aging process
Salminen, A., Kauppinen, A., & Kaarniranta, K. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1477-1 · Cited by 121
“white adipose tissue and increased thermogenesis are hallmarks of the activity of FGF21, thus being able to reduce obesity [82].”
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“FGF21 was shown to increase PGC-1α in liver and fat tissue (Potthoff et al. 2009; Fisher et al. 2012) and to regulate energy homeostasis in adipocytes via the SIRT1-PGC1 pathway (Chau et al. 2010).”
BackgroundER-associated degradation in health and disease – from substrate to organism
Bhattacharya, A., & Qi, L. (2019) · Journal of Cell Science · doi:10.1242/jcs.232850 · Cited by 109
“…Inagaki et al., 2008; Kharitonenkov et al., 2005; Owen et al., 2014), reduced female fertility (Owen et al., 2013), adipose tissue browning (BonDurant et al., 2017; Fisher et al., 2012; Hondares et al., 2010; Owen et al., 2014), and resistance to diet-induced obesity (Kharitonenkov et al., 2005).”
BackgroundFibroblast growth factors in cardiovascular disease: The emerging role of FGF21
Domouzoglou, E. M., Naka, K. Κ., Vlahos, A. P., Papafaklis, M. I., Michalis, L. K., Tsatsoulis, A., & Maratos–Flier, E. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00527.2015 · Cited by 115
Exercise Training Induces Depot-Specific Adaptations to White and Brown Adipose Tissue
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“Previous studies in rodents indicated that prWAT behaved similarly to pgWAT in response to a high-fat diet (Takahashi and Ide, 2000) or growth factors such as fibroblast growth factor 21 (Fisher et al., 2012).”
BackgroundBrown Adipose Tissue and Its Role in Insulin and Glucose Homeostasis
Maliszewska, K., & Kretowski, A. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041530 · Cited by 124
“In animals, following cold exposure, FGF21 expression was reduced in the liver (where it is produced), but enhanced in brown and white adipose tissue, where FGF21 enhances UCP1 expression and the browning of subcutaneous tissue [142].”
BackgroundMitochondrial stress and mitokines in aging
Burtscher, J., Soltany, A., Visavadiya, N. P., Burtscher, M., Millet, G. P., Khoramipour, K., & Khamoui, A. V. (2023) · Aging Cell · doi:10.1111/acel.13770 · Cited by 123
“…the autocrine action of FGF21 induces upregulation of the mitochondrial biogenesis marker proliferationactivated receptor co- activator 1 (PGC- 1α; Fisher et al., 2012), and via activation of adenosine monophosphate- activated protein kinase (AMPK) and sirtuin 1 (SIRT1) improves mitochondrial…”
BackgroundFGF21 Revolutions: Recent Advances Illuminating FGF21 Biology and Medicinal Properties
Kharitonenkov, A., & DiMarchi, R. D. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.09.007 · Cited by 114
“Thus, a few recent reports are suggestive that FGF21 produced in multiple tissues is acting in a local mode [15,17,23,28,68,69].”
Martins, F. F., Marinho, T. D. S., Cardoso, L. E. M., Barbosa‐da‐Silva, S., Souza‐Mello, V., Águila, M. B., & Mandarim‐de‐Lacerda, C. A. (2022) · Cell Biochemistry and Function · doi:10.1002/cbf.3751 · Cited by 120
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Targeting white, brown and perivascular adipose tissue in atherosclerosis development
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“fibroblast growth factor (FGF) 21 (Fisher et al., 2012), bone morphogenetic protein (BMP) 4 (Qian et al.”
BackgroundLipolytic and thermogenic depletion of adipose tissue in cancer cachexia
Tsoli, M., Swarbrick, M. M., & Robertson, G. R. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.10.039 · Cited by 113
Singhal, G., Fisher, F. M., Chee, M. J. S., Tan, T. G., Ouaamari, A. E., Adams, A. C., Najarían, R. M., Kulkarni, R., Benoist, C. O., Flier, J. S., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148252 · Cited by 112
Contreras, C., González‐García, I., Seoane‐Collazo, P., Martínez‐Sánchez, N., Liñares‐Pose, L., Rial‐Pensado, E., Fernø, J., Tena‐Sempere, M., Casals, N., Diéguez, C., et al. (2016) · Diabetes · doi:10.2337/db15-1547 · Cited by 114
“Brown adipocytes induced in WAT, also known as “beige” or “brite” cells (6,11,41), are derived from a precursor population distinct from both mature white and brown adipocytes (42,43).”
BackgroundRegulation of glucose homoeostasis by brown adipose tissue
Peirce, V. J., & Vidal‐Puig, A. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70055-x · Cited by 111
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“Expression of Ucp1 and Ppargc1a did not change with betaine in either BAT or eWAT, consistent with greater susceptibility of iWAT to browning stimuli (51) and Fgf21-mediated induction of thermogenic programs (28).”
BackgroundInflammatory Signaling and Brown Fat Activity
Omran, F., & Christian, M. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00156 · Cited by 111
Chronic AMPK activation via loss of FLCN induces functional beige adipose tissue through PGC-1α/ERRαPreprint
Yan, M., Audet‐Walsh, É., Manteghi, S., Dufour, C. R., Walker, B., Baba, M., St‐Pierre, J., Giguère, V., & Pause, A. (2016) · Genes & Development · doi:10.1101/gad.281410.116 · Cited by 111
“Notably, PRDM16, PPAR γ , and PGC-1 α have been shown to be critical determinants in the transcriptional control of mitochondrial and thermogenic genes during this transition (Seale et al. 2011; Kleiner et al. 2012).”
Kolumam, G., Chen, M. Z., Tong, R., Zavala-Solorio, J., Kates, L., van Bruggen, N., Ross, J., Wyatt, S. K., Gandham, V. D., Carano, R. A. D., et al. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.05.028 · Cited by 108
“In addition, FGF21 induces the emergence of UCP1-positive adipocytes in the white adipose tissue (WAT) depot, a process now termed browning (Fisher et al., 2012).”
BackgroundGeller, S., Arribat, Y., Netzahualcoyotzi, C., Lagarrigue, S., Carneiro, L., Zhang, L., Amati, F., López‐Mejía, I. C., & Pellerin, L. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.08.004 · Cited by 117
“…O2 consumption and browning of WAT by acting amongst others on the brain; increased food intake without a central action; and finally, increased serum FFAs by inducing lipolysis in WAT (Douris et al., 2015; Fisher et al., 2012; Inagaki et al., 2007; Véniant et al., 2015; Yilmaz et al., 2018).”
BackgroundCognitive and autonomic determinants of energy homeostasis in obesity
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Protein-dependent regulation of feeding and metabolism
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The Impact of Dietary Methionine Restriction on Biomarkers of Metabolic Health
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Beiging of white adipose tissue as a therapeutic strategy for weight loss in humans
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Loss of mitochondrial protease ClpP protects mice from diet‐induced obesity and insulin resistance
Bhaskaran, S., Pharaoh, G. A., Ranjit, R., Murphy, A., Matsuzaki, S., Nair, B. C., Forbes, B., Gispert, S., Auburger, G. W. J., Humphries, K. M., et al. (2018) · EMBO Reports · doi:10.15252/embr.201745009 · Cited by 107
“Stromal vascular fraction (SVF) from sWAT was differentiated to mature adipocytes as described before [27,60].”
Extreme Terrestrial Environments: Life in Thermal Stress and Hypoxia. A Narrative Review
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“Such mechanism also occurs in beige adipose tissue (Shabalina et al., 2013), whose formation is stimulated in the cold (Fisher et al., 2012) or by caloric restriction (Fabbiano et al., 2016).”
BackgroundThe Interplay Between Adipose Tissue and Vasculature: Role of Oxidative Stress in Obesity
Zhou, Y., Li, H., & Xia, N. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.650214 · Cited by 111
“Currently, there are a few well-known strategies that can induce browning in adipose tissues, which include cold acclimation and treatment of growth factors such as fibroblast growth factor 21 (FGF21) (132), atrial natriuretic peptide (ANP) (133), and bone morphogenetic protein (BMP) (134).”
BackgroundHuman 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 114
ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity
Fougerat, A., Schoiswohl, G., Polizzi, A., Régnier, M., Wagner, C., Smati, S., Fougeray, T., Lippi, Y., Lasserre, F., Raho, I., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110910 · Cited by 109
FGF21-receptor agonists: an emerging therapeutic class for obesity-related diseases
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Liu, J., Li, Y., Yang, P., Wan, J., Chang, Q., Wang, T. T. Y., Lu, W., Zhang, Y., Wang, Q., & Yu, L. L. (2017) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.7b03382 · Cited by 105
The Beige Adipocyte as a Therapy for Metabolic Diseases
Lizcano, F. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205058 · Cited by 110
“In obese and diabetic persons, the expansion through adipocyte hypertrophy is accompanied by a shift to an adverse adipokine secretory profile, which typically includes an elevated array of pro-inflammatory factors, such as TNF, IL-1β, IL-6, IL-8, resistin and monocyte chemoattractant protein 1 (MCP1), with a parallel…”
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Distinct populations of adipogenic and myogenic Myf5-lineage progenitors in white adipose tissues
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“an autocrine/paracrine inducer of thermogenic gene expression and beige phenotype in white adipose tissues (6), we examined FGF21 expression in sub-”
BackgroundInfluentialLow protein diets produce divergent effects on energy balance
Pezeshki, A., Zapata, R. C., Singh, A., Yee, N. J., & Chelikani, P. K. (2016) · Scientific Reports · doi:10.1038/srep25145 · Cited by 103
FGF21 promotes thermogenic gene expression as an autocrine factor in adipocytes
Abu-Odeh, M., Zhang, Y., Reilly, S. M., Ebadat, N., Keinan, O., Valentine, J. M., Hafezi-Bakhtiari, M., Ashayer, H., Mamoun, L., Zhou, X., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109331 · Cited by 106
“FGF21 induces efficient browning of iWAT (Fisher et al., 2012).”
InfluentialMetabolic fibroblast growth factors (FGFs): Mediators of energy homeostasis
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Singhal, V., Lawson, E. A., Ackerman, K. E., Fazeli, P. K., Clarke, H., Lee, H., Eddy, K. T., Marengi, D. A., Derrico, N. P., Bouxsein, M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100218 · Cited by 103
New therapeutic approaches for the treatment of obesity
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Mechanisms underlying UCP1 dependent and independent adipocyte thermogenesis
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The FGF21–adiponectin axis in controlling energy and vascular homeostasis
Hui, X. H., Feng, T., Liu, Q., Gao, Y., & Xu, A. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw013 · Cited by 103
IL-15 activates the Jak3/STAT3 signaling pathway to mediate glucose uptake in skeletal muscle cells
Krolopp, J. E., Thornton, S. M., & Abbott, M. J. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00626 · Cited by 104
Taniguchi, H., Tanisawa, K., Sun, X., Kubo, T., & Higuchi, M. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3308 · Cited by 104
“FGF21 is predominantly expressed in the liver (23), and it stimulates hepatic fatty acid oxidation (24), adipose tissue glucose uptake (25), adipose thermogenic gene expression, and browning of white adipose tissue (26) via classic FGF receptors complexed with -klotho in an endocrine or autocrine/paracrine manner (27–…”
FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation
Keinicke, H., Sun, G., Mentzel, C. M. J., Fredholm, M., John, L. M., Andersen, B., Raun, K., & Gerstenberg, M. K. (2020) · Endocrine Connections · doi:10.1530/ec-20-0152 · Cited by 104
“white adipose tissue to brown-fat like cells and increased the expression of thermogenic genes (49, 50).”
BackgroundLi, Y., Wong, K., Walsh, K. X., Gao, B., & Zang, M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.429852 · Cited by 101
Bowman, T. A., O’Keeffe, K. R., D’Aquila, T., Yan, Q. W., Griffin, J. D., Killion, E. A., Salter, D. M., Mashek, D. G., Buhman, K. K., & Greenberg, A. S. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.01.001 · Cited by 100
Traveling from the hypothalamus to the adipose tissue: The thermogenic pathway
Contreras, C., Nogueiras, R., Diéguez, C., Rahmouni, K., & López, M. (2017) · Redox Biology · doi:10.1016/j.redox.2017.04.019 · Cited by 104
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Brown Adipocytes Secrete GDF15 in Response to Thermogenic Activation
Campderrós, L., Moure, R., Cairó, M., Gavaldà‐Navarro, A., Quesada‐López, T., Cereijo, R., Giralt, M., Villarroya, J., & Villarroya, F. (2019) · Obesity · doi:10.1002/oby.22584 · Cited by 102
The mitochondrial unfolded protein response and mitohormesis: a perspective on metabolic diseases
Yi, H.-S., Chang, J. Y., & Shong, M. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-18-0005 · Cited by 99
Hill, C. M., Laeger, T., Albarado, D. C., McDougal, D. H., Berthoud, H.-R., Münzberg, H., & Morrison, C. D. (2017) · Scientific Reports · doi:10.1038/s41598-017-07498-w · Cited by 97
Activation of mTORC1 in skeletal muscle regulates whole-body metabolism through FGF21
Guridi, M., Tintignac, L. A. J., Lin, S., Kupr, B., Castets, P., & Rüegg, M. A. (2015) · Science Signaling · doi:10.1126/scisignal.aab3715 · Cited by 98
Understanding the brown adipocyte as a contributor to energy homeostasis
Chechi, K., Carpentier, A. C., & Richard, D. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.04.002 · Cited by 99
Yu, D., Yang, S. E., Miller, B. R., Wisinski, J. A., Sherman, D. S., Brinkman, J. A., Tomasiewicz, J. L., Richardson, N. E., Kimple, M. E., Cryns, V. L., et al. (2018) · The FASEB Journal · doi:10.1096/fj.201701211r · Cited by 95
Integrated stress response stimulates FGF21 expression: Systemic enhancer of longevity
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“Thus, FGF21 can enhance stress resistance by inducing thermogenesis and promoting the secretion of adipokines from BAT.”
BackgroundInfluentialIL-33-driven ILC2/eosinophil axis in fat is induced by sympathetic tone and suppressed by obesity
Ding, X., Luo, Y., Zhang, X., Zheng, H., Yang, X., Yang, X. O., & Liu, M. (2016) · Journal of Endocrinology · doi:10.1530/joe-16-0229 · Cited by 103
CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells
Jash, S., Banerjee, S., Lee, M., Farmer, S. R., & Puri, V. (2019) · iScience · doi:10.1016/j.isci.2019.09.011 · Cited by 96
“Progenitors isolated from subcutaneous white fat from children or adults can be induced to acquire a brite phenotype (Ahmadian et al., 2011; Fisher et al., 2012; Ohno et al., 2012), characterized by enhanced oxygen consumption and expression of uncoupling protein 1 (UCP1) and cell-death inducing…”
BackgroundImpaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle
Vandanmagsar, B., Warfel, J. D., Wicks, S. E., Ghosh, S., Salbaum, J. M., Burk, D., Dubuisson, O. S., Mendoza, T. M., Zhang, J., Noland, R. C., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.057 · Cited by 92
“Cpt1bm / Mice The pancreas and liver are both known producers and targets of FGF21 (Fon Tacer et al., 2010).”
Exercise and the Regulation of Adipose Tissue Metabolism
Tsiloulis, T., & Watt, M. J. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.06.016 · Cited by 103
Vargas‐Castillo, A., Fuentes‐Romero, R., Rodríguez-López, L. A., Torres, N., & Tovar, A. R. (2017) · Archives of Medical Research · doi:10.1016/j.arcmed.2017.10.002 · Cited by 101
Brown adipose tissue as a heat-producing thermoeffector
Nedergaard, J., & Cannon, B. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63912-7.00009-6 · Cited by 99
Cold 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 102
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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