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PRDM16 controls a brown fat/skeletal muscle switch
Open accessAbstract
Brown fat can increase energy expenditure and protect against obesity through a specialized program of uncoupled respiration. Here we show by in vivo fate mapping that brown, but not white, fat cells arise from precursors that express Myf5, a gene previously thought to be expressed only in the myogenic lineage. We also demonstrate that the transcriptional regulator PRDM16 (PRD1-BF1-RIZ1 homologous domain containing 16) controls a bidirectional cell fate switch between skeletal myoblasts and brown fat cells. Loss of PRDM16 from brown fat precursors causes a loss of brown fat characteristics and promotes muscle differentiation. Conversely, ectopic expression of PRDM16 in myoblasts induces their differentiation into brown fat cells. PRDM16 stimulates brown adipogenesis by binding to PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) and activating its transcriptional function. Finally, Prdm16-deficient brown fat displays an abnormal morphology, reduced thermogenic gene expression and elevated expression of muscle-specific genes. Taken together, these data indicate that PRDM16 specifies the brown fat lineage from a progenitor that expresses myoblast markers and is not involved in white adipogenesis.
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“Emerging evidence suggests that brown adipocytes located in different anatomical locations may arise from different developmental origins.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [92]
In the citing paper
“Most recently, lineage-tracing studies have indicated that myf5-expressing progenitors can give rise to both skeletal muscle and the preformed BAT, in the interscapular and peri-renal depots 92 (Figure 3).”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [92]
In the citing paper
“However, not all brown fat cells are derived from myf5-expressing progenitors. For example, the brown fat cells emerging in white fat in response to β3-adrenergic stimulation are not marked by the myf5-driven fluorescent protein 92.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [92]
In the citing paper
“Current data suggest that in rodents, PRDM16 plays an important role in specifying brown fat cell fate for the interscapular, but not systemic brown adipose depots 92.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [92]
In the citing paper
“The genetic program leading to brown adipose tissue development, and potentially to the high abundance of mitochondria, is initiated by the zinc-finger protein PRDM16 (202)(203)(204).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [203]
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Citations
Cites
Brown Adipose Tissue: Function and Physiological Significance
CANNON, B., & NEDERGAARD, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00015.2003 · Cited by 6,433
Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor
Tontonoz, P., Hu, E., & Spiegelman, B. M. (1994) · Cell · doi:10.1016/0092-8674(94)90006-x · Cited by 3,564
Self-citationCre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
Srinivas, S., Watanabe, T., Lin, C.-S., William, C. M., Tanabe, Y., Jessell, T. M., & Costantini, F. (2001) · BMC Developmental Biology · doi:10.1186/1471-213x-1-4 · Cited by 3,121
15-Deoxy-Δ12,14-Prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ
FORMAN, B. M., Tontonoz, P., Chen, J., Brun, R. P., Spiegelman, B. M., & Evans, R. M. (1995) · Cell · doi:10.1016/0092-8674(95)90193-0 · Cited by 2,857
Self-citationPPARγ Is Required for the Differentiation of Adipose Tissue In Vivo and In Vitro
Rosen, E. D., Sarraf, P., Troy, A. E., Bradwin, G., Moore, K. J., Milstone, D. S., Spiegelman, B. M., & Mortensen, R. M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80211-7 · Cited by 2,081
Self-citationPPARγ Is Required for Placental, Cardiac, and Adipose Tissue Development
Barak, Y., Nelson, M. C., Ong, E. S., Jones, Y., Ruiz‐Lozano, P., Chien, K. R., Koder, A., & Evans, R. M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80209-9 · Cited by 1,983
Unexpected evidence for active brown adipose tissue in adult humans
Nedergaard, J., Bengtsson, T., & Cannon, B. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00691.2006 · Cited by 1,824
Developmental Origin of Fat: Tracking Obesity to Its Source
Gesta, S., Tseng, Y.-H., & Kahn, C. R. (2007) · Cell · doi:10.1016/j.cell.2007.10.004 · Cited by 1,508
Asymmetric self-renewal and commitment of satellite stem cells in muscle
Kuang, S., Kuroda, K., Le Grand, F., & Rudnicki, M. A. (2007) · Cell · doi:10.1016/j.cell.2007.03.044 · Cited by 1,449
Self-citationMolecular Regulation of Adipogenesis
Rosen, E. D., & Spiegelman, B. M. (2000) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.16.1.145 · Cited by 1,310
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–200 of 1,008
Lowe, C. E., O’Rahilly, S., & Rochford, J. J. (2011) · Journal of Cell Science · doi:10.1242/jcs.079699 · Cited by 353
Beige adipocyte maintenance is regulated by autophagy-induced mitochondrial clearance
Altshuler-Keylin, S., Shinoda, K., Hasegawa, Y., Ikeda, K., Hong, H., Kang, Q., Yang, Y., Perera, R. M., Debnath, J., & Kajimura, S. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.002 · Cited by 349
“Furthermore, classical brown adipocytes develop prenatally from a dermomyotome population marked by Engrailed-1, Myf5, and Pax7, whereas beige adipocytes arise postnatally fromprogenitor populations in WAT expressing Ebf2, Pdgfra, and Sca1 (Atit et al., 2006; Lee et al., 2012b; Sanchez-Gurmaches et al., 2012; Schulz e…”
BackgroundInfluentialThe developmental origins of adipose tissue
Berry, D. C., Stenesen, D., Zeve, D., & Graff, J. M. (2013) · Development · doi:10.1242/dev.080549 · Cited by 365
“…a variety of studies have been directed towards elucidating the molecular cascades and factors underlying brown fat formation, with the aim of triggering cells to have BAT-like energy-consuming actions (Cannon and Nedergaard, 2004; Kajimura et al., 2010; Seale et al., 2008; Seale et al., 2009).”
BackgroundTRPV4 Is a Regulator of Adipose Oxidative Metabolism, Inflammation, and Energy Homeostasis
Li, Y., Kleiner, S., Wu, J., Sah, R., Gupta, R. K., Banks, A. S., Cohen, P., Khandekar, M. J., Boström, P., Mepani, R. J., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.034 · Cited by 353
“These cells do not come from a myf5-positive lineage (Seale et al., 2008) and have been called beige or brite fat cells (Ishibashi and Seale, 2010; Petrovic et al., 2010).”
InfluentialSelf-citationIshibashi, J., & Seale, P. (2010) · Science · doi:10.1126/science.1190816 · Cited by 356
Self-citationSánchez-Gurmaches, J., Hung, C., Sparks, C. A., Tang, Y., Li, H., & Guertin, D. A. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.003 · Cited by 360
“In vivo fate mapping experiments further suggest that brown fat originates from a mesenchymal precursor cell that expresses the myogenic transcription factor Myf5 (Atit et al., 2006; Seale et al., 2008).”
BackgroundMethodInfluentialTranscriptional and epigenetic control of brown and beige adipose cell fate and function
Inagaki, T., Sakai, J., & Kajimura, S. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.62 · Cited by 347
Self-citationPPARs: diverse regulators in energy metabolism and metabolic diseases
Wang, Y.-X. (2010) · Cell Research · doi:10.1038/cr.2010.13 · Cited by 366
Vishvanath, L., MacPherson, K. A., Hepler, C., Wang, Q. A., Shao, M., Spurgin, S. B., Wang, M. Y., Kusminski, C. M., Morley, T. S., & Gupta, R. K. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.10.018 · Cited by 326
EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex
Ohno, H., Shinoda, K., Ohyama, K., Sharp, L. Z., & Kajimura, S. (2013) · Nature · doi:10.1038/nature12652 · Cited by 334
Self-citationTransplantation of adipose tissue and stem cells: role in metabolism and disease
Tran, T. T., & Kahn, C. R. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.20 · Cited by 335
“The first type of progenitor cell is present in interscapular brown adipose tissue, expresses myogenic factor 5 (Myf5), a regulatory factor expressed in muscle-cell precursors”
BackgroundTissue Stem Cells: Architects of Their Niches
Fuchs, E., & Blau, H. M. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.09.011 · Cited by 332
Sarjeant, K., & Stephens, J. M. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008417 · Cited by 328
Prdm3 and Prdm16 are H3K9me1 Methyltransferases Required for Mammalian Heterochromatin Integrity
Pinheiro, I., Margueron, R., Shukeir, N., Eisold, M., Fritzsch, C., Richter, F. M., Mittler, G., Genoud, C., Goyama, S., Kurokawa, M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.048 · Cited by 340
Baskaran, P., Krishnan, V., Ren, J. T., & Thyagarajan, B. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13514 · Cited by 325
“It is well known that PRDM-16 is a determinant of brown adipocyte lineage, which causes browning of WAT (Seale et al., 2008).”
BackgroundEvidence against a Beneficial Effect of Irisin in Humans
Raschke, S., Elsen, M., Gassenhuber, J., Sommerfeld, M. R., Schwahn, U., Brockmann, B., Jung, R., Wisløff, U., Tjønna, A. E., Raastad, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073680 · Cited by 327
Brown Adipose Tissue Energy Metabolism in Humans
Carpentier, A. C., Blondin, D. P., Virtanen, K. A., Richard, D., Haman, F., & Turcotte, É. E. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00447 · Cited by 338
IRF4 Is a Key Thermogenic Transcriptional Partner of PGC-1α
Kong, X., Banks, A. S., Liu, T., Kazak, L., Rao, R. R., Cohen, P., Wang, X., Yu, S., Lo, J. C., Tseng, Y., et al. (2014) · Cell · doi:10.1016/j.cell.2014.04.049 · Cited by 308
“These two UCP1+ cell types derive from different embryological origins, and they express overlapping but distinct gene expression programs (Seale et al., 2008; Wu et al., 2012).”
Self-citationPerivascular Adipose Tissue in Vascular Function and Disease
Brown, N. K., Zhou, Z., Zhang, J., Zeng, R., Wu, J., Eitzman, D. T., Chen, Y., & Chang, L. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303029 · Cited by 313
Implications of nonshivering thermogenesis for energy balance regulation in humans
Lichtenbelt, W. D. V. M., & Schrauwen, P. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00652.2010 · Cited by 318
Mir193b–365 is essential for brown fat differentiation
Sun, L., Xie, H., Mori, M. A., Alexander, R., Yuan, B., Hattangadi, S. M., Liu, Q., Kahn, C. R., & Lodish, H. F. (2011) · Nature Cell Biology · doi:10.1038/ncb2286 · Cited by 313
“Although for decades it was believed that brown adipocytes and white adipocytes share a common progenitor, a lineage-tracing study has demonstrated that brown adipocytes arise from a Myf5 (myogenic factor 5)-positive, myoblastic lineag”
Irisin: A Hope in Understanding and Managing Obesity and Metabolic Syndrome
Arhire, L. I., Mihalache, L., & Covașă, M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00524 · Cited by 317
Yin, H., Pasut, A., Soleimani, V. D., Bentzinger, C. F., Antoun, G., Thorn, S., Seale, P., Fernando, P., van IJcken, W., Grosveld, F., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.01.004 · Cited by 293
“By contrast, brown adipocytes are specialized to dissipate energy in the form of body heat (thermogenesis) and are characterized by expression of uncoupling protein Ucp1 in their abundant mitochondria (Frontini and Cinti, 2010).”
BackgroundResultInfluentialSelf-citationAdipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways
Ambele, M. A., Dhanraj, P., Giles, R., & Pepper, M. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124283 · Cited by 302
Transcriptional control of brown adipocyte development and physiological function—of mice and menPreprint
Seale, P., Kajimura, S., & Spiegelman, B. M. (2009) · Genes & Development · doi:10.1101/gad.1779209 · Cited by 295
“Consistent with this, BAT from PRDM16-deficient mice at embryonic day 17 exhibits an abnormal morphology with dramatically reduced expression of thermogenic genes and elevated expression of muscle-specific genes (Seale et al. 2008).”
BackgroundInfluentialSelf-citationHondares, E., Rosell, M., Díaz-Delfín, J., Olmos, Y., Monsalve, M., Iglesias, R., Villarroya, F., & Giralt, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.252775 · Cited by 302
A stringent validation of mouse adipose tissue identity markers
de Jong, J. M. A., Larsson, O. S., Cannon, B., & Nedergaard, J. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00023.2015 · Cited by 303
microRNAs in the Regulation of Adipogenesis and Obesity
McGregor, R. A., & Choi, M. (2011) · Current Molecular Medicine · doi:10.2174/156652411795677990 · Cited by 287
Chi, J., Wu, Z., Choi, C. H. J., Nguyen, L., Tegegne, S., Ackerman, S. E., Crane, A., Marchildon, F., Tessier-Lavigne, M., & Cohen, P. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.12.011 · Cited by 285
miR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit
Chen, Y., Siegel, F., Kipschull, S., Haas, B., Fröhlich, H., Meister, G., & Pfeifer, A. (2013) · Nature Communications · doi:10.1038/ncomms2742 · Cited by 282
Cellular origins of cold‐induced brown adipocytes in adult mice
Lee, Y., Petkova, A. P., Konkar, A. A., & Granneman, J. G. (2014) · The FASEB Journal · doi:10.1096/fj.14-263038 · Cited by 291
Rodríguez, A., Ezquerro, S., Méndez-Giménez, L., Becerril, S., & Frühbeck, G. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00297.2015 · Cited by 287
The prdm family: expanding roles in stem cells and development
Hohenauer, T., & Moore, A. W. (2012) · Development · doi:10.1242/dev.070110 · Cited by 265
“3B) (Kajimura et al., 2009; Seale et al., 2009; Seale et al., 2007).”
Pharmacological and nutritional agents promoting browning of white adipose tissue
Bonet, M. L., Oliver, P., & Palou, A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.12.002 · Cited by 286
Wang, S., Liang, X., Yang, Q., Fu, X., Rogers, C. J., Zhu, M. J., Rodgers, B. D., Jiang, Q., Dodson, M. V., & Du, . (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.23 · Cited by 285
Giordano, A., Smorlesi, A., Frontini, A., Barbatelli, G., & Cinti, S. (2014) · European Journal of Endocrinology · doi:10.1530/eje-13-0945 · Cited by 298
AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue
Steculorum, S. M., Ruud, J., Karakasilioti, I., Backes, H., Engström, L., Timper, K., Hess, M. E., Tsaousidou, E., Mauer, J., Vogt, M. C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.044 · Cited by 293
“…from a Myf-5-positive lineage, which can give rise either to myocytes or brown adipocytes and b adrenergic stimulation can potently direct their gene expression profile and differentiation toward the brown adipocyte lineage (Kajimura et al., 2009; Seale et al., 2008; Timmons et al., 2007).”
BackgroundHOCKING, S. L., Samocha‐Bonet, D., Milner, K., Greenfield, J. R., & Chisholm, D. J. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1041 · Cited by 295
“These cells are distinct from brown adipocytes, which are derived from myogenic precursors expressing Myf-5, and are located in classic locations including the perinephric and interscapular fat pads (146, 147).”
BackgroundDistinction of white, beige and brown adipocytes derived from mesenchymal stem cells
Park, A. (2014) · World Journal of Stem Cells · doi:10.4252/wjsc.v6.i1.33 · Cited by 291
Mitochondrial (Dys)function in Adipocyte (De)differentiation and Systemic Metabolic Alterations
Pauw, A. D., Tejerina, S., Raes, M. J., Keijer, J., & Arnould, T. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.081155 · Cited by 278
Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity
Janesick, A., & Blumberg, B. (2011) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.20197 · Cited by 276
“…cell lines (e.g., 3T3-L1, 3T3-F442A), or primary cells that were already committed to the adipocyte fate and would not easily differentiate into any other lineage (like bone, cartilage, muscle, or even brown fat) (Cornelius et al., 1994; Timmons et al., 2007; Park et al., 2008; Seale et al., 2008).”
BackgroundAdipocyte lineages: Tracing back the origins of fat
Sánchez-Gurmaches, J., & Guertin, D. A. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.05.027 · Cited by 277
“satellite cells ingWAT and pgWAT negative [116,117]”
BackgroundTGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue
Velazquez-Villegas, L. A., Perino, A., Lemos, V., Zietak, M., Nomura, M., Pols, T. W. H., & Schoonjans, K. (2018) · Nature Communications · doi:10.1038/s41467-017-02068-0 · Cited by 268
MyomiR-133 regulates brown fat differentiation through Prdm16
Trajkovski, M., Ahmed, K., Esau, C., & Stoffel, M. (2012) · Nature Cell Biology · doi:10.1038/ncb2612 · Cited by 263
“intensity (log) Fold-change Cutoff (–1, 2) Cutoff (1, 2)”
InfluentialButler, A. A., & Kozak, L. P. (2010) · Diabetes · doi:10.2337/db09-1471 · Cited by 265
The origin of intermuscular adipose tissue and its pathophysiological implications
Vettor, R., Milan, G., Franzin, C., Sanna, M., Coppi, P. D., Rizzuto, R., & Federspil, G. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00229.2009 · Cited by 274
Brown and beige fat: Molecular parts of a thermogenic machine
Cohen, P., & Spiegelman, B. M. (2015) · Diabetes · doi:10.2337/db15-0318 · Cited by 259
“Conversely, the UCP1 cells induced in subcutaneous white fat depots by cold or b-adrenergic agonists come from a myf5(2) lineage (10).”
BackgroundOrexin Is Required for Brown Adipose Tissue Development, Differentiation, and Function
Sellayah, D., Bharaj, P., & Sikder, D. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.010 · Cited by 259
Krings, A., Rahman, S., Huang, S., Lu, Y., Czernik, P. J., & Lecka‐Czernik, B. (2011) · Bone · doi:10.1016/j.bone.2011.06.016 · Cited by 266
“In neonates, brown adipocytes originate from precursor cells, which express myogenic factor Myf5, and may also differentiate to muscle [32].”
Propagation of adipogenic signals through an epigenomic transition statePreprint
Steger, D. J., Grant, G. R., Schupp, M., Tomaru, T., Lefterova, M. I., Schug, J., Manduchi, E., Stoeckert, C. J., & Lazar, M. A. (2010) · Genes & Development · doi:10.1101/gad.1907110 · Cited by 259
“Recent studies implicating PRDM16 and CEBPb in brown fat differentiation from myoblastic precursors used a GR ligand for in vitro differentiation (Seale et al. 2008; Kajimura et al. 2009).”
BackgroundHuman Multipotent Adipose-Derived Stem Cells Differentiate into Functional Brown Adipocytes
Elabd, C., Chiellini, C., Carmona, M., Galitzky, J., Cochet, O., Petersen, R., Pénicaud, L., Kristiansen, K., Bouloumié, A., Casteilla, L., et al. (2009) · Stem Cells · doi:10.1002/stem.200 · Cited by 252
Programming human pluripotent stem cells into white and brown adipocytes
Ahfeldt, T., Schinzel, R. T., Lee, Y., Hendrickson, D. G., Kaplan, A. N., Lum, D. H., Camahort, R., Xia, F., Shay, J., Rhee, E. P., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2411 · Cited by 256
Brown fat biology and thermogenesis
Richard, D. (2010) · Frontiers in bioscience · doi:10.2741/3786 · Cited by 251
“There is now compelling evidence (6-9, 35) to suggest that brown adipocytes from classical BAT depots share their precursor cells with myocytes (Figure 1).”
BackgroundResultInfluentialFat cells directly sense temperature to activate thermogenesis
Li, Y., Wu, J., Cohen, P., Kazak, L., Khandekar, M. J., Jedrychowski, M. P., Zeng, X., Gygi, S. P., & Spiegelman, B. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310261110 · Cited by 250
“Recently, it has been shown that these beige cells have a developmental origin (14, 15) and molecular signature (12) that is distinct from that of classic brown adipocytes.”
BackgroundSelf-citationLodhi, I. J., Yin, L., Jensen-Urstad, A. P. L., Funai, K., Coleman, T., Baird, J. H., Ramahi, M. K. E., Razani, B., Song, H., Hsu, F., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.013 · Cited by 253
“Moreover, PPARγ is thought to promote fat development at the expense of myogenesis (Hu et al., 1995; Seale et al., 2008).”
BackgroundDirect lineage conversions: unnatural but useful?
Vierbuchen, T., & Wernig, M. (2011) · Nature Biotechnology · doi:10.1038/nbt.1946 · Cited by 259
Dempersmier, J. M., Sambeat, A., Gulyaeva, О. N., Paul, S. M., Hudak, C. S. S., Raposo, H. F., Kwan, H. Y., Kang, C., Wong, R. H.-F., & Sul, H. S. (2015) · Molecular Cell · doi:10.1016/j.molcel.2014.12.005 · Cited by 246
Ma, S., Yu, H., Zhao, Z., Luo, Z., Chen, J., Ni, Y., Jin, R., Ma, L., Wang, P., Zhu, Z., et al. (2012) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjs001 · Cited by 241
“PR-domain-containing 16 (PRDM16) (Seale et al., 2008) and BMP7 (Tseng et al., 2008) have been recently identified as molecular switches that determine the formation and function of brown adipocytes.”
BackgroundThe on-off switches of the mitochondrial uncoupling proteins
Azzu, V., & Brand, M. D. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.11.001 · Cited by 239
“1 kg of fat per year [31], the recent discovery of a molecular switch for BAT production could provide another potential drug target for increasing BAT mass in humans [33].”
BackgroundYang, Q., Liang, X., Sun, X., Zhang, L., Fu, X., Rogers, C. J., Berim, A., Zhang, S., Wang, S., Wang, B., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.010 · Cited by 237
Proteome Differences between Brown and White Fat Mitochondria Reveal Specialized Metabolic Functions
Forner, F., Kumar, C., Luber, C. A., Fromme, T., Klingenspor, M., & Mann, M. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.014 · Cited by 238
“BAT and muscle have the capacity to perform adaptive thermogenesis, and recently it has been shown that brown fat cells and muscle cells, but not white fat cells, derive from the same lineage (Atit et al., 2006; Seale et al., 2008; Timmons et al., 2007).”
BackgroundResultGalmozzi, A., Mitro, N., Ferrari, A., Gers, E., Gilardi, F., Godio, C., Cermenati, G., Gualerzi, A., Donetti, E., Rotili, D., et al. (2012) · Diabetes · doi:10.2337/db12-0548 · Cited by 242
“This browning occurred in the absence of a change in expression of Prdm16, a major determinant of interscapular brown fat development (38).”
BackgroundWeighing in on Adipocyte Precursors
Berry, R., Jeffery, E. C., & Rodeheffer, M. S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.10.003 · Cited by 246
Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders
Kim, S. H., & Plutzky, J. (2016) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2016.40.1.12 · Cited by 240
Convertible visceral fat as a therapeutic target to curb obesity
Giordano, A., Frontini, A., & Cinti, S. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.31 · Cited by 241
A Long Noncoding RNA Transcriptional Regulatory Circuit Drives Thermogenic Adipocyte Differentiation
Zhao, X.-Y., Li, S., Wang, G.-X., Yu, Q., & Lin, J. D. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.06.004 · Cited by 231
“In rodents, brown and beige fats appear to have distinct developmental origins (Berry and Rodeheffer, 2013; Seale et al., 2008; Timmons et al., 2007; Wu et al., 2012) and are differentially influenced by genetic factors (Kozak and Koza, 2010; Xue et al., 2007).”
Shao, M., Ishibashi, J., Kusminski, C. M., Wang, Q. A., Hepler, C., Vishvanath, L., MacPherson, K. A., Spurgin, S. B., Sun, K., Holland, W. L., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.023 · Cited by 223
“Brown adipocytes are organized into distinct depots and originate developmentally from a Myf5+ lineage (Seale et al., 2008).”
Self-citationBrown adipose tissue and thermogenesis
Fenzl, A., & Kiefer, F. W. (2014) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2014-0022 · Cited by 239
“Kajimura S, Seale P, Tomaru T, Erdjument-Bromage H, Cooper MP, Ruas JL, Chin S, Tempst P, Lazar MA, Spiegelman BM. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex.”
BackgroundInfluentialPerivascular adipose tissue (PVAT) in atherosclerosis: a double-edged sword
Qi, X.-Y., Qu, S.-L., Xiong, W., Rom, O., Chang, L., & Jiang, Z. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0777-x · Cited by 239
Bertholet, A. M., Kazak, L., Chouchani, E. T., Bogaczyńska, M. G., Paranjpe, I., Wainwright, G. L., Bétourné, A., Kajimura, S., Spiegelman, B. M., & Kirichok, Y. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.002 · Cited by 225
“Despite their morphological and functional similarities, beige and brown adipocytes have clearly distinct developmental origins (Long et al., 2014; Rosen and Spiegelman, 2014; Seale et al., 2008).”
Self-citationBrown Adipose Tissue Controls Skeletal Muscle Function via the Secretion of Myostatin
Kong, X., Yao, T. S., Zhou, P., Kazak, L., Tenen, D. E., Lyubetskaya, A., Dawes, B. A., Tsai, L. T.-Y., Kahn, B. B., Spiegelman, B. M., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.07.004 · Cited by 223
Self-citationSIRT1 Deacetylase in POMC Neurons Is Required for Homeostatic Defenses against Diet-Induced Obesity
Ramadori, G., Fujikawa, T., Fukuda, M., Anderson, J. G., Morgan, D. A., Mostoslavsky, R., Stuart, R. C., Perelló, M., Vianna, C. R., Nillni, E. A., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.05.010 · Cited by 226
A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate
Wang, W., Ishibashi, J., Trefely, S., Shao, M., Cowan, A. J., Sakers, A. P., Lim, H., O’Connor, S., Doan, M. T., Cohen, P., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.05.005 · Cited by 223
“PRDM16 binds and regulates the expression of many genes involved in FAO, likely via co-activating the transcriptional function of PPARs, including PPARa, a key driver of FAO in many cell types (Harms et al., 2015; Hondares et al., 2011; Seale et al., 2008).”
Self-citationPrdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress
Chuikov, S., Levi, B. P., Smith, M. L., & Morrison, S. J. (2010) · Nature Cell Biology · doi:10.1038/ncb2101 · Cited by 229
Human Brown Adipose Tissue: What We Have Learned So Far
Betz, M. J., & Enerbäck, S. (2015) · Diabetes · doi:10.2337/db15-0146 · Cited by 223
“Beige adipocytes exhibit the same cell morphology as classic brown adipocytes and appear to be functionally equal (18), but do not originate from Myf5-expressing progenitors (19) and exhibit unique gene signatures that differ from those of classic brown adipocytes found in the interscapular BAT (20).”
BackgroundEbf2 is a selective marker of brown and beige adipogenic precursor cells
Wang, W., Kissig, M., Rajakumari, S., Huang, L., Lim, H., Won, K., & Seale, P. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1412685111 · Cited by 222
“WAT do not originate from Myf5-lineage precursor cells (2, 14, 17, 20, 24, 29).”
BackgroundSelf-citationThe role of skeletal‐muscle‐based thermogenic mechanisms in vertebrate endothermy
Rowland, L. A., Bal, N. C., & Periasamy, M. (2014) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12157 · Cited by 233
Adipose tissue plasticity from WAT to BAT and in between
Lee, Y., Mottillo, E. P., & Granneman, J. G. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.05.011 · Cited by 236
“(BRITE) [160] or beige [39], it is not clear whether these various designations refer to the same cell type [56, 150, 160, 161].”
BackgroundEmerging Complexities in Adipocyte Origins and Identity
Sánchez-Gurmaches, J., Hung, C., & Guertin, D. A. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.01.004 · Cited by 225
“Is there a brite/beige adipocyte lineage?—Myf5/Pax3-Cre lineage tracing experiments indicate that brite adipocytes in the inguinal scWAT do not arise from a Myf5/ Pax3 lineage [49, 56, 58].”
BackgroundHeterogeneity of adipose tissue in development and metabolic function
Schöttl, T., Kapser-Fischer, I., & Ussar, S. (2018) · Journal of Experimental Biology · doi:10.1242/jeb.162958 · Cited by 228
“…adipocytespecific genes, such as UCP1, Cidea, Pgc1α and PAT2 (Harms and Seale, 2013; Ussar et al., 2014), beige and brown adipocytes appear to develop from different embryonic precursor populations (Seale et al., 2008) with a unique gene expression signature (Ussar et al., 2014; Xue et al., 2007).”
BackgroundInfluentialWhite-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma
Frontini, A., Vitali, A., Perugini, J., Murano, I., Romiti, C., Ricquier, D., Guerrieri, M., & Cinti, S. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.02.005 · Cited by 218
“[18] Thus, we cannot distinguish brown adipocytes in the interscapular area from those in the inter-renal area on the basis of Myf5 lineage in addition to their morphology and physiology.”
BackgroundDistinct and dynamic myogenic populations in the vertebrate embryo
BUCKINGHAM, M. E., & Vincent, S. D. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.08.001 · Cited by 215
Retinaldehyde dehydrogenase 1 regulates a thermogenic program in white adipose tissue
Kiefer, F. W., Vernochet, C., O’Brien, P., Spoerl, S., Brown, J. D., Nallamshetty, S., Zeyda, M., Stulnig, T. M., Cohen, D. E., Kahn, C. R., et al. (2012) · Nature Medicine · doi:10.1038/nm.2757 · Cited by 210
ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes
Ussar, S., Lee, K. Y., Dankel, S. N., Boucher, J., Haering, M.-F., Kleinridders, A., Thomou, T., Xue, R., Macotela, Y., Cypess, A. M., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008490 · Cited by 216
Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes
Lo, K. A., & Sun, L. (2013) · Bioscience Reports · doi:10.1042/bsr20130046 · Cited by 225
Molecular and Cellular Regulation of Skeletal Myogenesis
Comai, G., & Tajbakhsh, S. (2014) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-405943-6.00001-4 · Cited by 213
Cohen, P., & Spiegelman, B. M. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-10-0749 · Cited by 217
“from a skeletal muscle–like lineage, as marked by Myf5 or Pax7 (Seale et al., 2008; Lepper and Fan, 2010).”
BackgroundSelf-citationZhang, H., Zhu, L., Bai, M., Liu, Y., Zhan, Y., Deng, T., Yang, H., Sun, W., Wang, X., Zhu, K., et al. (2018) · International Journal of Cancer · doi:10.1002/ijc.31977 · Cited by 211
“PR domain containing 16 (PRDM16), a zinc finger transcription factor, has been proposed to be a bidirectional cell fate switch that promotes BAT differentiation.(20,21) Loss of PRDM16 function results in myogenic differentiation of preadipocytes isolated from BAT, while gain of PRDM16 function leads to the genesis of…”
BackgroundRetractedSpecialization Can Drive the Evolution of Modularity
Espinosa‐Soto, C., & Wagner, A. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000719 · Cited by 211
“. Another example involves the cellular level. Mammalian brown fat cells share some traits and gene activity patterns with white fat cells, and others with muscle cells”
BackgroundCharacterization of Cre recombinase models for the study of adipose tissue
Jeffery, E. C., Berry, R., CHURCH, C. D., Yu, S., Shook, B. A., Horsley, V., Rosen, E. D., & Rodeheffer, M. S. (2014) · Adipocyte · doi:10.4161/adip.29674 · Cited by 215
Shengchen, W., Jing, L., Yujie, Y., Yue, W., & Xu, S. (2021) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2021.125962 · Cited by 209
Brown Adipose Tissue in Adult Humans: A Metabolic Renaissance
Lee, P. C., Swarbrick, M. M., & Ho, K. K. Y. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1081 · Cited by 224
PRDM proteins: important players in differentiation and disease
Fog, C. K., Galli, G. G., & Lund, A. H. (2012) · BioEssays · doi:10.1002/bies.201100107 · Cited by 201
Sequence-specific regulator Prdm14 safeguards mouse ESCs from entering extraembryonic endoderm fates
Ma, Z., Swigut, T., Valouev, A., Rada-Iglesias, Á., & Wysocka, J. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2000 · Cited by 203
Brown and Beige Adipose Tissue and Aging
Zoico, E., Rubele, S., Caro, A. D., Nori, N., Mazzali, G., Fantin, F., Rossi, A. P., & Zamboni, M. M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00368 · Cited by 219
Leiria, L. O., Wang, C., Lynes, M. D., Yang, K., Shamsi, F., Sato, M. M., Sugimoto, S., Chen, E. Y.-S., Bussberg, V., Narain, N. R., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.07.001 · Cited by 205
“The highmetabolic capacity of thermogenic fat ismediated by a tightly controlled transcriptional and post-transcriptional regulatory system (Seale et al., 2008; Chouchani et al., 2016; Lynes et al., 2017; Bartelt et al., 2018).”
BackgroundArndt, A.-K., Schäfer, S., Drenckhahn, J., Sabeh, M. K., Plovie, E. R., Caliebe, A., Klopocki, E., Musso, G. A., Werdich, A. A., Kalwa, H., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.05.015 · Cited by 203
Lee, J., Park, Y.-K., Park, S., Jang, Y., Waring, N. A., Dey, A., Ozato, K., Lai, B., Peng, W., & Ge, K. (2017) · Nature Communications · doi:10.1038/s41467-017-02403-5 · Cited by 209
Zamani, N., & Brown, C. (2010) · Endocrine Reviews · doi:10.1210/er.2010-0018 · Cited by 214
Madsen, L., Pedersen, L. M., Lillefosse, H. H., Fjære, E., Brønstad, I., Hao, Q., Petersen, R. K., Hallenborg, P., Ma, T., Matteis, R. D., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011391 · Cited by 204
“and classic brown adipocytes arise from Myf5 expressing progenitors”
Metadata
- Authors
- Seale, P., Bjork, B., Yang, W., Kajimura, S., Chin, S., Kuang, S., Scimè, A., Devarakonda, S., Conroe, H. M., Erdjument-Bromage, H., Tempst, P., Rudnicki, M. A., Beier, D. R., & Spiegelman, B. M.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Spiegelman, Bruce M.
- ORCID
- Venue
- Nature
- Published
- 2008-08
- Volume
- 454
- Issue
- 7207
- Pages
- 961-967
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2583329
- OpenAlex
- W2104827888
- Cited by
- 2,347
- References
- 44
- Citations by year
- 2026: 77 · 2025: 71 · 2024: 118 · 2023: 115 · 2022: 129 · 2021: 134 · 2020: 141 · 2019: 134 · 2018: 168 · 2017: 165 · 2016: 139 · 2015: 167 · 2014: 157 · 2013: 181 · 2012: 134
- FWCI
- 71.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- American Heart Association
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK031405)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR044031)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- PRDM16, brown adipose tissue, skeletal muscle, Myf5, brown adipogenesis, PPARγ, thermogenesis, myogenesis, energy expenditure, obesity
- MeSH terms
- Animals, Adipose Tissue, Brown, Cell Differentiation, Cell Line, Chlorocebus aethiops, DNA-Binding Proteins, Male, Transcription Factors, Muscle, Skeletal, Gene Expression Regulation, Developmental, COS Cells, Muscle Development, PPAR gamma, Mice, Myogenic Regulatory Factor 5, Adipocytes, Brown, Adipocytes, White
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