Chronic Peroxisome Proliferator-activated Receptor γ (PPARγ) Activation of Epididymally Derived White Adipocyte Cultures Reveals a Population of Thermogenically Competent, UCP1-containing Adipocytes Molecularly Distinct from Classic Brown Adipocytes
Open accessAbstract
The recent insight that brown adipocytes and muscle cells share a common origin and in this respect are distinct from white adipocytes has spurred questions concerning the origin and molecular characteristics of the UCP1-expressing cells observed in classic white adipose tissue depots under certain physiological or pharmacological conditions. Examining precursors from the purest white adipose tissue depot (epididymal), we report here that chronic treatment with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone promotes not only the expression of PGC-1alpha and mitochondriogenesis in these cells but also a norepinephrine-augmentable UCP1 gene expression in a significant subset of the cells, providing these cells with a genuine thermogenic capacity. However, although functional thermogenic genes are expressed, the cells are devoid of transcripts for the novel transcription factors now associated with classic brown adipocytes (Zic1, Lhx8, Meox2, and characteristically PRDM16) or for myocyte-associated genes (myogenin and myomirs (muscle-specific microRNAs)) and retain white fat characteristics such as Hoxc9 expression. Co-culture experiments verify that the UCP1-expressing cells are not proliferating classic brown adipocytes (adipomyocytes), and these cells therefore constitute a subset of adipocytes ("brite" adipocytes) with a developmental origin and molecular characteristics distinguishing them as a separate class of cells.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
When stimulated by PPARγ agonist, brown fat cells emerging in white fat express molecular characteristics distinct from the interscapular brown fat cells.
“When stimulated by PPARγ agonist, they express molecular characteristics distinct from the interscapular brown fat cells 93.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [93]
Cites
Brown Adipose Tissue: Function and Physiological Significance
CANNON, B., & NEDERGAARD, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00015.2003 · Cited by 6,433 · see citing works
Self-citationIdentification and Importance of Brown Adipose Tissue in Adult Humans
Cypess, A. M., Lehman, S., Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y.-H., Doria, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810780 · Cited by 4,399 · see citing works
Cold-Activated Brown Adipose Tissue in Healthy Men
van Marken Lichtenbelt, W. D., Vanhommerig, J. W., Smulders, N. M., Drossaerts, J. M. A. F. L., Kemerink, G. J., Bouvy, N. D., Schrauwen, P., & Teule, G. J. J. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808718 · Cited by 3,452 · see citing works
Peroxisome Proliferator-Activated Receptors: Nuclear Control of Metabolism
Desvergne, B., & Wahli, W. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.5.0380 · Cited by 3,079 · see citing works
Functional Brown Adipose Tissue in Healthy Adults
Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., Taittonen, M., Laine, J., Savisto, N.-J., Enerbäck, S., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808949 · Cited by 3,058 · see citing works
PRDM16 controls a brown fat/skeletal muscle switch
Seale, P., Bjork, B., Yang, W., Kajimura, S., Chin, S., Kuang, S., Scimè, A., Devarakonda, S., Conroe, H. M., Erdjument-Bromage, H., et al. (2008) · Nature · doi:10.1038/nature07182 · Cited by 2,347 · see citing works
High Incidence of Metabolically Active Brown Adipose Tissue in Healthy Adult Humans
Saito, M., Okamatsu-Ogura, Y., Matsushita, M., Watanabe, K., Yoneshiro, T., Nio-Kobayashi, J., Iwanaga, T., Miyagawa, M., Kameya, T., Nakada, K., et al. (2009) · Diabetes · doi:10.2337/db09-0530 · Cited by 1,848 · see citing works
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 · see citing works
Self-citationMice lacking mitochondrial uncoupling protein are cold-sensitive but not obese
Enerbäck, S., Jacobsson, A., Simpson, E. M., Guerra, C., Yamashita, H., Harper, M.-E., & Kozak, L. P. (1997) · Nature · doi:10.1038/387090a0 · Cited by 1,379 · see citing works
Feldmann, H. M., Golozoubova, V., Cannon, B., & Nedergaard, J. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.12.014 · Cited by 1,318 · see citing works
Self-citationMyogenin, a factor regulating myogenesis, has a domain homologous to MyoD
Wright, W. E., Sassoon, D. A., & Lin, V. K. (1989) · Cell · doi:10.1016/0092-8674(89)90583-7 · Cited by 1,309 · see citing works
Transcriptional Control of Brown Fat Determination by PRDM16
Seale, P., Kajimura, S., Yang, W., Chin, S., Rohas, L. M., Uldry, M., Tavernier, G., Langin, D., & Spiegelman, B. M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.06.001 · Cited by 1,174 · see citing works
White Fat Progenitor Cells Reside in the Adipose Vasculature
Tang, W., Zeve, D., Suh, J. M., Bosnakovski, D., Kyba, M., Hammer, R. E., Tallquist, M. D., & Graff, J. M. (2008) · Science · doi:10.1126/science.1156232 · Cited by 1,113 · see citing works
Timmons, J. A., Wennmalm, K., Larsson, O., Walden, T. B., Lassmann, T., Petrovic, N., Hamilton, D. L., Gimeno, R. E., Wahlestedt, C., Baar, K., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610615104 · Cited by 732 · see citing works
Self-citationZingaretti, M. C., Crosta, F., Vitali, A., Guerrieri, M., Frontini, A., Cannon, B., Nedergaard, J., & Cinti, S. (2009) · The FASEB Journal · doi:10.1096/fj.09-133546 · Cited by 725 · see citing works
Self-citationCousin, B., Cinti, S., Morroni, M., Raimbault, S., Ricquier, D., Pénicaud, L., & Casteilla, L. (1992) · Journal of Cell Science · doi:10.1242/jcs.103.4.931 · Cited by 665 · see citing works
Guerra, C., Koza, R. A., Yamashita, H., Walsh, K., & Kozak, L. P. (1998) · Journal of Clinical Investigation · doi:10.1172/jci3155 · Cited by 635 · see citing works
Evidence for a role of developmental genes in the origin of obesity and body fat distribution
Gesta, S., Blüher, M., Yamamoto, Y., Norris, A. W., Berndt, J., Kralisch, S., Boucher, J., Lewis, C. R., & Kahn, C. R. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601752103 · Cited by 617 · see citing works
Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone.
Wilson-Fritch, L., Nicoloro, S., Chouinard, M., Lazar, M. A., Chui, P. C., Leszyk, J., Straubhaar, J., Czech, M. P., & Corvera, S. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21752 · Cited by 616 · see citing works
Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes
Himms-Hagen, J., Melnyk, A., Zingaretti, M. C., Ceresi, E., Barbatelli, G., & Cinti, S. (2000) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2000.279.3.c670 · Cited by 593 · see citing works
Cederberg, A., Grønning, L. M., Åhrén, B., Taskén, K., Carlsson, P., & Enerbäck, S. (2001) · Cell · doi:10.1016/s0092-8674(01)00474-3 · Cited by 555 · see citing works
Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold
Golozoubova, V., Hohtola, E., Matthias, A., Jacobsson, A., Cannon, B., & Nedergaard, J. (2001) · The FASEB Journal · doi:10.1096/fj.00-0536fje · Cited by 503 · see citing works
Self-citationAcquirement of brown fat cell features by human white adipocytes
Tiraby, C., Tavernier, G., Lefort, C., Larrouy, D., Bouillaud, F., Ricquier, D., & Langin, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305235200 · Cited by 474 · see citing works
Cidea-deficient mice have lean phenotype and are resistant to obesity
Zhou, Z., Toh, S. Y., Chen, Z., Guo, K., Ng, C. P., Ponniah, S., Lin, S., Hong, W., & Li, P. (2003) · Nature Genetics · doi:10.1038/ng1225 · Cited by 468 · see citing works
Pioglitazone Induces Mitochondrial Biogenesis in Human Subcutaneous Adipose Tissue In Vivo
Bogacka, I., Xie, H., Bray, G. A., & Smith, S. R. (2005) · Diabetes · doi:10.2337/diabetes.54.5.1392 · Cited by 467 · see citing works
Wilson-Fritch, L., Burkart, A., Bell, G., Mendelson, K., Leszyk, J., Nicoloro, S., Czech, M., & Corvera, S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.3.1085-1094.2003 · Cited by 459 · see citing works
MicroRNA-206: The skeletal muscle-specific myomiR
McCarthy, J. J. (2008) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2008.03.001 · Cited by 423 · see citing works
β-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse
Atit, R., Sgaier, S. K., Mohamed, O. A., Taketo, M. M., Dufort, D., Joyner, A. L., Niswander, L., & Conlon, R. A. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.04.449 · Cited by 400 · see citing works
Transdifferentiation properties of adipocytes in the adipose organ
Cinti, S. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00183.2009 · Cited by 379 · see citing works
Hypoxia-Independent Angiogenesis in Adipose Tissues during Cold Acclimation
Xue, Y., Petrovič, N., Cao, R., Larsson, O. S., Lim, S., Chen, S., Feldmann, H. M., Liang, Z., Zhu, Z., Nedergaard, J., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.11.009 · Cited by 379 · see citing works
Self-citationNuclear receptor corepressor RIP140 regulates fat accumulation
Leonardsson, G., Steel, J. H., Christian, M., Pocock, V., Milligan, S., Bell, J., So, P.-W., Medina-Gomez, G., Vidal-Puig, A., White, R., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401013101 · Cited by 366 · see citing works
Thermogenic Responses in Brown Fat Cells Are Fully UCP1-dependent
Matthias, A., Ohlson, K. B. E., Fredriksson, J. M., Jacobsson, A., Nedergaard, J., & Cannon, B. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000547200 · Cited by 342 · see citing works
Self-citationRong, J. X., Qiu, Y., Hansen, M. K., Zhu, L., Zhang, V., Xie, M., Okamoto, Y., Mattie, M. D., Higashiyama, H., Asano, S., et al. (2007) · Diabetes · doi:10.2337/db06-1135 · Cited by 335 · see citing works
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 289 · see citing works
Xue, B., Rim, J.-S., Hogan, J. C., Coulter, A. A., Koza, R. A., & Kozak, L. P. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m600287-jlr200 · Cited by 288 · see citing works
Hansen, J. B., Jørgensen, C., Petersen, R. K., Hallenborg, P., De Matteis, R., Bøye, H. A., Petrovic, N., Enerbäck, S., Nedergaard, J., Cinti, S., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0301964101 · Cited by 287 · see citing works
Self-citationAlmind, K., Manieri, M., Sivitz, W. I., Cinti, S., & Kahn, C. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610416104 · Cited by 286 · see citing works
UCP1 is essential for adaptive adrenergic nonshivering thermogenesis
Golozoubova, V., Cannon, B., & Nedergaard, J. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00387.2005 · Cited by 255 · see citing works
Self-citationNordström, E. A., Rydén, M., Backlund, E. C., Dahlman, I. A., Kaaman, M., Blomqvist, L., Cannon, B., Nedergaard, J., & Arner, P. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1726 · Cited by 190 · see citing works
Self-citationA Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle
Crisan, M., Casteilla, L., Lehr, L., Carmona, M., Paoloni-Giacobino, A., Yap, S., Sun, B., Léger, B., Logar, A., Pénicaud, L., et al. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0325 · Cited by 172 · see citing works
Fukui, Y., Masui, S., Osada, S., Umesono, K., & Motojima, K. (2000) · Diabetes · doi:10.2337/diabetes.49.5.759 · Cited by 168 · see citing works
Molecular determinants of brown adipocyte formation and function: Figure 1.
Farmer, S. R. (2008) · Genes & Development · doi:10.1101/gad.1681308 · Cited by 165 · see citing works
Shabalina, I. G., Jacobsson, A., Cannon, B., & Nedergaard, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402375200 · Cited by 162 · see citing works
Self-citationEsser, V., Brown, N. F., Cowan, A. T., Foster, D. W., & McGarry, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.12.6972 · Cited by 157 · see citing works
Distinct expression of muscle‐specific MicroRNAs (myomirs) in brown adipocytes
Waldén, T. B., Timmons, J. A., Keller, P., Nedergaard, J., & Cannon, B. (2008) · Journal of Cellular Physiology · doi:10.1002/jcp.21621 · Cited by 157 · see citing works
Self-citationDevelopment of brown fat cells in monolayer culture
Néchad, M., Kuusela, P., Carneheim, C., Björntorp, P. A., Nedergaard, J., & Cannon, B. (1983) · Experimental Cell Research · doi:10.1016/0014-4827(83)90384-1 · Cited by 154 · see citing works
Self-citationLaplante, M., Sell, H., MacNaul, K. L., Richard, D., Berger, J. P., & Deshaies, Y. (2003) · Diabetes · doi:10.2337/diabetes.52.2.291 · Cited by 153 · see citing works
Li, P., Zhu, Z., Lu, Y., & Granneman, J. G. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00010.2005 · Cited by 143 · see citing works
Digby, J. E., Montague, C. T., Sewter, C. P., Sanders, L., Wilkison, W. O., O'Rahilly, S., & Prins, J. B. (1998) · Diabetes · doi:10.2337/diab.47.1.138 · Cited by 134 · see citing works
Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARγ agonist
Petrovič, N., Shabalina, I. G., Timmons, J. A., Cannon, B., & Nedergaard, J. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00035.2008 · Cited by 134 · see citing works
Self-citationSell, H., Berger, J. P., Samson, P., Castriota, G. A., Lalonde, J., Deshaies, Y., & Richard, D. (2004) · Endocrinology · doi:10.1210/en.2004-0321 · Cited by 130 · see citing works
Epididymal white adipose tissue after cold stress in rats II. Mitochondrial changes
Lonćar, D., Afzelius, B. A., & Cannon, B. (1988) · Journal of Ultrastructure and Molecular Structure Research · doi:10.1016/0889-1605(88)90010-9 · Cited by 111 · see citing works
Self-citationPuigserver, P., Herron, D. K., Gianotti, M., Palou, A., Cannon, B., & Nedergaard, J. (1992) · Biochemical Journal · doi:10.1042/bj2840393 · Cited by 107 · see citing works
Self-citationTvrdík, P., Asadi, A., Kozak, L. P., Nedergaard, J., Cannon, B., & Jacobsson, A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.50.31738 · Cited by 106 · see citing works
Self-citationThe Importance of Brown Adipose Tissue
Timmons, J. A., & Pedersen, B. K. (2009) · New England Journal of Medicine · doi:10.1056/nejmc091009 · Cited by 84 · see citing works
Self-citationEpididymal white adipose tissue after cold stress in rats I. Nonmitochondrial changes
Lonćar, D., Afzelius, B. A., & Cannon, B. (1988) · Journal of Ultrastructure and Molecular Structure Research · doi:10.1016/0889-1605(88)90001-8 · Cited by 80 · see citing works
Self-citationCannon, B., & Nedergaard, J. (2008) · Nature · doi:10.1038/454947a · Cited by 73 · see citing works
Self-citationSkála, J. P., Barnard, T., & Lindberg, O. (1970) · Comparative Biochemistry and Physiology · doi:10.1016/0010-406x(70)90368-3 · Cited by 65 · see citing works
Moulin, K., Truel, N., André, M., ARNAULD, E., Nibbelink, M. M., Cousin, B., Dani, C., Pénicaud, L., & Casteilla, L. (2001) · Biochemical Journal · doi:10.1042/bj3560659 · Cited by 59 · see citing works
Carmona, M. C., Louche, K., Lefebvre, B., Pilon, A., Hennuyer, N., Audinot-Bouchez, V., Fiévet, C., Torpier, G., Formstecher, P., Renard, P., et al. (2007) · Diabetes · doi:10.2337/db06-1734 · Cited by 51 · see citing works
Shabalina, I. G., Backlund, E. C., Bar‐Tana, J., Cannon, B., & Nedergaard, J. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.04.038 · Cited by 41 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Brown and beige fat: Development, function and therapeutic potential
Harms, M., & Seale, P. (2013) · Nature Medicine · doi:10.1038/nm.3361 · Cited by 2,328 · see citing works
PPARγ signaling and metabolism: the good, the bad and the future
Ahmadian, M., Suh, J. M., Hah, N., Liddle, C., Atkins, A. R., Downes, M., & Evans, R. M. (2013) · Nature Medicine · doi:10.1038/nm.3159 · Cited by 2,016 · see citing works
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529 · see citing works
FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis
Fisher, F. M., Kleiner, S., Douris, N., Fox, E. C., Mepani, R. J., Verdeguer, F., Wu, J., Kharitonenkov, A., Flier, J. S., Maratos-Flier, E., et al. (2012) · Genes & Development · doi:10.1101/gad.177857.111 · Cited by 1,478 · see citing works
Adipose tissue browning and metabolic health
Bartelt, A., & Heeren, J. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.204 · Cited by 1,177 · see citing works
Adaptive thermogenesis in adipocytes: Is beige the new brown?
Wu, J., Cohen, P., & Spiegelman, B. M. (2013) · Genes & Development · doi:10.1101/gad.211649.112 · Cited by 828 · see citing works
PPARs in Obesity-Induced T2DM, Dyslipidaemia and NAFLD
Gross, B., Pawlak, M., Lefebvre, P., & Staels, B. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.135 · Cited by 778 · see citing works
Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans
Lee, P., Linderman, J. D., Smith, S., Brychta, R. J., Wang, J., Idelson, C., Perron, R. M., Werner, C. D., Phan, G. Q., Kammula, U. S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.017 · Cited by 802 · see citing works
Zhang, Y., Li, R., Meng, Y., Li, S., Donelan, W., Zhao, Y., Qi, L., Zhang, M., Wang, X., Cui, T., et al. (2014) · Diabetes · doi:10.2337/db13-1106 · Cited by 733 · see citing works
“These brown fat cells, UCP-1 positive, are designated as beige or brown-in-white (brite) cells (11,34).”
BackgroundProtection from obesity and diabetes by blockade of TGF-β/smad3 signaling
Yadav, H., Quijano, C., Kamaraju, A. K., Gavrilova, O., Malek, R., Chen, W., Zerfas, P., Zhigang, D., Wright, E. C., Stuelten, C., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.04.013 · Cited by 709 · see citing works
Nonshivering thermogenesis and its adequate measurement in metabolic studies
Cannon, B., & Nedergaard, J. (2011) · Journal of Experimental Biology · doi:10.1242/jeb.050989 · Cited by 677 · see citing works
Self-citationRoberts, L. D., Boström, P., O’Sullivan, J. F., Schinzel, R. T., Lewis, G. D., Dejam, A., Lee, Y.-K., Palma, M. J., Calhoun, S., Georgiadi, A., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.003 · Cited by 643 · see citing works
Cellular bioenergetics as a target for obesity therapy
Tseng, Y.-H., Cypess, A. M., & Kahn, C. R. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3138 · Cited by 591 · see citing works
Norheim, F., Langleite, T. M., Hjorth, M., Holen, T., Kielland, A., Stadheim, H. K., Gulseth, H. L., Birkeland, K. I., Jensen, J., & Drevon, C. A. (2014) · The FEBS Journal · doi:10.1111/febs.12619 · Cited by 563 · see citing works
Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction
Jiang, C., Xie, C., Lv, Y., Li, J., Krausz, K. W., Shi, J., Brocker, C. N., Desai, D., Amin, S. G., Bisson, W. H., et al. (2015) · Nature Communications · doi:10.1038/ncomms10166 · Cited by 559 · see citing works
Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues
Pellegrinelli, V., Carobbio, S., & Vidal-Puig, A. (2016) · Diabetologia · doi:10.1007/s00125-016-3933-4 · Cited by 432 · see citing works
Fitzgibbons, T. P., & Czech, M. P. (2014) · Journal of the American Heart Association · doi:10.1161/jaha.113.000582 · Cited by 331 · see citing works
Sarjeant, K., & Stephens, J. M. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008417 · Cited by 328 · see citing works
Lowered testosterone in male obesity: Mechanisms, morbidity and management
Grossmann, M., Tang Fui, M., & Dupuis, P. (2014) · Asian Journal of Andrology · doi:10.4103/1008-682x.122365 · Cited by 293 · see citing works
Essential Role for miR-196a in Brown Adipogenesis of White Fat Progenitor Cells
Mori, M., Nakagami, H., Rodriguez-Araujo, G., Nimura, K., & Kaneda, Y. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001314 · Cited by 243 · see citing works
Xin, C., Liu, J., Zhang, J., Zhu, D., Wang, H., Xiong, L., Lee, Y., Ye, J., Lian, K., Xu, C., et al. (2016) · International Journal of Obesity · doi:10.1038/ijo.2015.199 · Cited by 248 · see citing works
Induction of Adipose Tissue Browning as a Strategy to Combat Obesity
Kuryłowicz, A., & Puzianowska-Kuźnicka, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176241 · Cited by 219 · see citing works
Trayhurn, P., Drevon, C. A., & Eckel, J. (2011) · Archives of Physiology and Biochemistry · doi:10.3109/13813455.2010.535835 · Cited by 214 · see citing works
Low brown adipose tissue activity in endurance-trained compared with lean sedentary men
Vosselman, M. J., Hoeks, J., Brans, B., Pallubinsky, H., Nascimento, E. B. M., van der Lans, A. A. J. J., Broeders, E. P. M., Mottaghy, F. M., Schrauwen, P., & van Marken Lichtenbelt, W. D. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.130 · Cited by 193 · see citing works
The Sense of Smell Impacts Metabolic Health and Obesity
Riera, C. E., Tsaousidou, E., Halloran, J., Follett, P., Hahn, O., Pereira, M. M. A., Ruud, L. E., Alber, J., Tharp, K., Anderson, C. M., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.015 · Cited by 191 · see citing works
Hypoxia and Adipocyte Physiology: Implications for Adipose Tissue Dysfunction in Obesity
Trayhurn, P. (2014) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071812-161156 · Cited by 194 · see citing works
Targeting fatty acid metabolism to improve glucose metabolism
Stinkens, R., Goossens, G. H., Jocken, J. W. E., & Blaak, E. E. (2015) · Obesity Reviews · doi:10.1111/obr.12298 · Cited by 183 · see citing works
Brown adipose tissue: Development, metabolism and beyond
Schulz, T. J., & Tseng, Y.-H. (2013) · Biochemical Journal · doi:10.1042/bj20130457 · Cited by 173 · see citing works
Adipose tissues and thyroid hormones
Obregon, M.-J. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00479 · Cited by 167 · see citing works
Irisin as a muscle-derived hormone stimulating thermogenesis – A critical update
Hofmann, T., Elbelt, U., & Stengel, A. (2014) · Peptides · doi:10.1016/j.peptides.2014.01.016 · Cited by 162 · see citing works
Myokines mediate the cross talk between skeletal muscle and other organs
Chen, W., Wang, L., You, W., & Shan, T. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30033 · Cited by 162 · see citing works
Fibroblast growth factor 21 and browning of white adipose tissue
Cuevas-Ramos, D., Mehta, R., & Aguilar-Salinas, C. A. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00037 · Cited by 149 · see citing works
Boucher, J., Mori, M. A., Lee, K. Y., Smyth, G., Liew, C. W., Macotela, Y., Rourk, M., Bluher, M., Russell, S. J., & Kahn, C. R. (2012) · Nature Communications · doi:10.1038/ncomms1905 · Cited by 142 · see citing works
Brown Adipose Tissue as a Regulator of Energy Expenditure and Body Fat in Humans
Saito, M. (2013) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2013.37.1.22 · Cited by 146 · see citing works
de Jong, J. M. A., Sun, W., Pires, N. D., Frontini, A., Balaz, M., Jespersen, N. Z., Feizi, A., Petrovic, K., Fischer, A. W., Bokhari, M. H., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0101-4 · Cited by 137 · see citing works
Zuriaga, M. A., Fuster, J. J., Gokce, N., & Walsh, K. (2017) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2017.00027 · Cited by 122 · see citing works
Exercise induces white adipose tissue browning across the weight spectrum in humans
Otero-Díaz, B., Rodríguez-Flores, M., Sánchez-Muñoz, V., Monraz-Preciado, F., Ordoñez-Ortega, S., Becerril-Elias, V., Baay-Guzmán, G., Obando-Monge, R., García-García, E., Palacios-González, B., et al. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01781 · Cited by 110 · see citing works
HDAC11 suppresses the thermogenic program of adipose tissue via BRD2
Bagchi, R. A., Ferguson, B. S., Stratton, M. S., Hu, T., Cavasin, M. A., Sun, L., Lin, Y.-H., Liu, D., Londono, P., Song, K., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.120159 · Cited by 110 · see citing works
Zhu, Y., Gao, Y., Tao, C., Shao, M., Zhao, S., Huang, W., Yao, T., Johnson, J. A., Liu, T., Cypess, A. M., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.005 · Cited by 100 · see citing works
Effects of exercise on brown and beige adipocytes
Dewal, R. S., & Stanford, K. I. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2018.04.013 · Cited by 92 · see citing works
No evidence of white adipocyte browning after endurance exercise training in obese men
Tsiloulis, T., Carey, A. L., Bayliss, J., Canny, B., Meex, R. C. R., & Watt, M. J. (2018) · International Journal of Obesity · doi:10.1038/ijo.2017.295 · Cited by 70 · see citing works
Salomäki, H., Heinäniemi, M., Vähätalo, L. H., Ailanen, L., Eerola, K., Ruohonen, S. T., Pesonen, U., & Koulu, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115778 · Cited by 63 · see citing works
Insights into brown adipose tissue evolution and function from non-model organisms
Jastroch, M., Oelkrug, R., & Keipert, S. (2018) · Journal of Experimental Biology · doi:10.1242/jeb.169425 · Cited by 55 · see citing works
Leibel, R. L., Seeley, R. J., Darsow, T., Berg, E. G., Smith, S. R., & Ratner, R. (2015) · Diabetes · doi:10.2337/db15-0004 · Cited by 52 · see citing works
Dinas, P. C., Lahart, I. M., Timmons, J. A., Svensson, P.-A., Koutedakis, Y., Flouris, A. D., & Metsios, G. S. (2017) · F1000Research · doi:10.12688/f1000research.11107.2 · Cited by 51 · see citing works
Self-citationDistel, E., Penot, G., Cadoudal, T., Balguy, I., Durant, S., & Benelli, C. (2012) · Biochimie · doi:10.1016/j.biochi.2012.04.014 · Cited by 49 · see citing works
Augmenting energy expenditure by mitochondrial uncoupling: A role of AMP-activated protein kinase
Klaus, S., Keipert, S., Rossmeisl, M., & Kopecky, J. (2012) · Genes & Nutrition · doi:10.1007/s12263-011-0260-8 · Cited by 44 · see citing works
Pervin, S., Reddy, S. T., & Singh, R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.653179 · Cited by 42 · see citing works
Adrenergically stimulated blood flow in brown adipose tissue is not dependent on thermogenesis
Abreu-Vieira, G., Hagberg, C. E., Spalding, K. L., Cannon, B., & Nedergaard, J. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00494.2014 · Cited by 34 · see citing works
Self-citationPereira, M. P., Ferreira, L. A. A., da Silva, F. H. S., Christoffolete, M. A., Metsios, G. S., Chaves, V. E., de França, S. A., Damazo, A. S., Flouris, A. D., & Kawashita, N. H. (2017) · Nutrition · doi:10.1016/j.nut.2017.05.007 · Cited by 24 · see citing works
Hypothalamic control of adipose tissue
Stefanidis, A., Wiedmann, N. M., Adler, E. S., & Oldfield, B. J. (2014) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2014.08.001 · Cited by 22 · see citing works
- Authors
- Petrovic, N., Walden, T. B., Shabalina, I. G., Timmons, J. A., Cannon, B., & Nedergaard, J.
- Affiliations
- Stockholm University (SE)
- Royal Veterinary College (GB)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 285
- Issue
- 10
- Pages
- 7153-7164
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2844165
- OpenAlex
- W1979026577
- Cited by
- 1,263
- References
- 61
- Citations by year
- 2026: 21 · 2025: 29 · 2024: 39 · 2023: 44 · 2022: 67 · 2021: 85 · 2020: 94 · 2019: 79 · 2018: 99 · 2017: 118 · 2016: 111 · 2015: 114 · 2014: 114 · 2013: 121 · 2012: 63
- FWCI
- 28.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Funders
- European Commission (201100)
- Vetenskapsrådet
- Biotechnology and Biological Sciences Research Council (BB/G013128/1)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- PPARγ, rosiglitazone, brown adipocytes, beige adipocytes, thermogenesis, UCP1, epididymal adipose tissue, PGC-1α, mitochondrial biogenesis, adipocyte precursors, PRDM16, HOXC9, norepinephrine, adipogenesis
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Uncoupling Protein 1, Rosiglitazone, Animals, Cell Differentiation, Cells, Cultured, Epididymis, Gene Expression Regulation, Hypoglycemic Agents, Ion Channels, Male, Mice, Inbred C57BL, Oxygen Consumption, Transcription Factors, Biomarkers, Trans-Activators, Mice, Knockout, Coculture Techniques, Thermogenesis, Mitochondrial Proteins, Thiazolidinediones, PPAR gamma, Voltage-Dependent Anion Channels, Mice, Adipocytes, Brown, Adipocytes, White
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review