Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation
Open accessAbstract
Adipocyte precursor cells give raise to two major cell populations with different physiological roles: white and brown adipocytes. Here we demonstrate that the retinoblastoma protein (pRB) regulates white vs. brown adipocyte differentiation. Functional inactivation of pRB in wild-type mouse embryo fibroblasts (MEFs) and white preadipocytes by expression of simian virus 40 large T antigen results in the expression of the brown fat-specific uncoupling protein 1 (UCP-1) in the adipose state. Retinoblastoma gene-deficient ( Rb – / – ) MEFs and stem cells, but not the corresponding wild-type cells, differentiate into adipocytes with a gene expression pattern and mitochondria content resembling brown adipose tissue. pRB-deficient MEFs exhibit an increased expression of the Forkhead transcription factor Foxc2 and its target gene cAMP-dependent protein kinase regulatory subunit RIα, resulting in increased cAMP sensitivity. Suppression of cAMP-dependent protein kinase activity in Rb –/– MEFs blocked the brown adipocyte-like gene expression pattern without affecting differentiation per se . Immunohistochemical studies revealed that pRB is present in the nuclei of white but not brown adipocyte precursor cells at a developmental stage where both cell types begin to accumulate lipid and brown adipocytes express UCP-1. Furthermore, pRB rapidly undergoes phosphorylation upon cold-induced neodifferentiation and up-regulation of UCP-1 expression in brown adipose tissue. Finally, down-regulation of pRB expression accompanies transdifferentiation of white into brown adipocytes in response to β3-adrenergic receptor agonist treatment. We propose that pRB acts as a molecular switch determining white vs. brown adipogenesis, suggesting a previously uncharacterized function of this key cell cycle regulator in adipocyte lineage commitment and differentiation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Proteins of the retinoblastoma family and necdin selectively inhibit brown preadipocyte differentiation.
“Among the known inhibitors of preadipocyte-adipocyte transition, proteins of the retinoblastoma (Rb) family, and necdin, a growth repressor functionally resembling Rb, selectively inhibit brown preadipocyte differentiation 132,133,168”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [132]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139 · see citing works
Self-citationA Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81410-5 · Cited by 3,864 · see citing works
Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators
Issemann, I., & Green, S. (1990) · Nature · doi:10.1038/347645a0 · Cited by 3,519 · see citing works
PPARγ 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 · see citing works
Transcriptional regulation of adipogenesisPreprint
Rosen, E. D., Walkey, C. J., Puigserver, P., & Spiegelman, B. M. (2000) · Genes & Development · doi:10.1101/gad.14.11.1293 · Cited by 1,902 · see citing works
Towards a molecular understanding of adaptive thermogenesis
Lowell, B. B., & Spiegelman, B. M. (2000) · Nature · doi:10.1038/35007527 · Cited by 1,630 · see citing works
Mitochondrial transcription factor A is necessary for mtDNA maintance and embryogenesis in mice
Larsson, N.-G., Wang, J., Wilhelmsson, H., Oldfors, A., Rustin, P., Lewandoski, M., Barsh, G. S., & Clayton, D. A. (1998) · Nature Genetics · doi:10.1038/ng0398-231 · Cited by 1,594 · see citing works
CREB regulates hepatic gluconeogenesis through the coactivator PGC-1
Herzig, S., Long, F., Jhala, U. S., Hedrick, S., Quinn, R., Bauer, A., Rudolph, D., Schutz, G., Yoon, C., Puigserver, P., et al. (2001) · Nature · doi:10.1038/35093131 · Cited by 1,440 · see citing works
The Rb/E2F pathway: expanding roles and emerging paradigms
Harbour, J. W., & Dean, D. C. (2000) · Genes & Development · doi:10.1101/gad.813200 · Cited by 1,153 · see citing works
Development of obesity in transgenic mice after genetic ablation of brown adipose tissue
Lowell, B. B., S-Susulic, V., Hamann, A., Lawitts, J. A., Himms-Hagen, J., Boyer, B. B., Kozak, L. P., & Flier, J. S. (1993) · Nature · doi:10.1038/366740a0 · Cited by 1,075 · see citing works
Nuclear activators and coactivators in mammalian mitochondrial biogenesis
Scarpulla, R. C. (2002) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(02)00343-3 · Cited by 631 · 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
Self-citationCederberg, 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
Self-citationLin, J., Puigserver, P., Donovan, J., Tarr, P., & Spiegelman, B. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c100631200 · Cited by 552 · see citing works
SRC-1 and TIF2 Control Energy Balance between White and Brown Adipose Tissues
Picard, F., Géhin, M., Annicotte, J., Rocchi, S., Champy, M., O’Malley, B. W., Chambon, P., & Auwerx, J. H. (2002) · Cell · doi:10.1016/s0092-8674(02)01169-8 · Cited by 444 · see citing works
Chen, P., Riley, D. J., Chen, Y., & Lee, W. (1996) · Genes & Development · doi:10.1101/gad.10.21.2794 · Cited by 442 · see citing works
Dannenberg, J.-H., van Rossum, A., Schuijff, L., & te Riele, H. (2000) · Genes & Development · doi:10.1101/gad.847700 · Cited by 413 · see citing works
The retinoblastoma gene family in differentiation and development
Lipinski, M. M., & Jacks, T. (1999) · Oncogene · doi:10.1038/sj.onc.1203244 · Cited by 404 · see citing works
Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance
Ricquier, D., & Bouillaud, F. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.00003.x · Cited by 385 · see citing works
Cellular transformation by SV40 large T antigen: interaction with host proteins
Ali, S. H., & DeCaprio, J. A. (2001) · Seminars in Cancer Biology · doi:10.1006/scbi.2000.0342 · Cited by 367 · see citing works
Adipocyte differentiation and transdifferentiation: plasticity of the adipose organ.
Cinti, S. (2002) · Journal of Endocrinological Investigation · doi:10.1007/bf03344046 · Cited by 213 · see citing works
Hansen, J., Zhang, H., Rasmussen, T. H., Petersen, R., Flindt, E., & Kristiansen, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m005567200 · Cited by 187 · see citing works
Self-citationHansen, J. B., Petersen, R. K., Larsen, B. M., Bártková, J., Alsner, J., & Kristiansen, K. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.4.2386 · Cited by 143 · see citing works
Self-citationIn vitro and in vivo induction of brown adipocyte uncoupling protein (thermogenin) by retinoic acid
Puigserver, P., Vázquez, F., Bonet, M. L., Picó, C., & Palou, A. (1996) · Biochemical Journal · doi:10.1042/bj3170827 · Cited by 125 · see citing works
Ross, S. R., Choy, L., Graves, R. A., Fox, N. W., SOLEVEVA, V., Klaus, S., Ricquier, D., & Spiegelman, B. M. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7561 · Cited by 121 · see citing works
Cherington, V., Morgan, B. A., Spiegelman, B. M., & Roberts, T. M. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.12.4307 · Cited by 91 · see citing works
Rohlfs, E. M., Daniel, K. W., Premont, R. T., Kozak, L. P., & Collins, S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.18.10723 · Cited by 85 · see citing works
A thyroid hormone receptor coactivator negatively regulated by the retinoblastoma protein
Chang, K., Chen, Y., Chen, T.-T., Chou, W., Chen, P., Ma, Y.-Y., Yang‐Feng, T. L., Leng, X., Tsai, M., O’Malley, B. W., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.17.9040 · Cited by 77 · see citing works
Houštěk, J., Kopecký, J., Rychter, Z., & Soukup, T. (1988) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(88)90103-x · Cited by 69 · see citing works
DNA synthesis in mouse brown adipose tissue is under β-adrenergic control
Rehnmark, S., & Nedergaard, J. (1989) · Experimental Cell Research · doi:10.1016/0014-4827(89)90086-4 · Cited by 64 · see citing works
Self-citationMoulin, 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
Higgins, C. M. J., Chatterjee, S., & Cherington, V. (1996) · Journal of Virology · doi:10.1128/jvi.70.2.745-752.1996 · Cited by 40 · see citing works
Adrenergic regulation of the mitochondrial uncoupling protein gene in brown fat tumor cells
Kozak, U. C., Held, W., Kreutter, D. K., & Kozak, L. P. (1992) · Molecular Endocrinology · doi:10.1210/mend.6.5.1603085 · Cited by 39 · see citing works
Hansen, J., Petersen, R., Jørgensen, C., & Kristiansen, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203870200 · Cited by 39 · see citing works
Self-citationBenito, M., Porrás, A., & Santos, E. (1993) · Experimental Cell Research · doi:10.1006/excr.1993.1308 · Cited by 28 · see citing works
Masuda, N., Yasumo, H., Furusawa, T., Tsukamoto, T., Sadano, H., & Osumi, T. (1998) · Gene · doi:10.1016/s0378-1119(98)00461-2 · Cited by 23 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [2]Rosen, E. D., Walkey, C. J., Puigserver, P. & Spiegelman, B. M. (2000) Genes Dev. 14**,** 1293–1307. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10837022/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Genes%20Dev.&volume=14&publication_year=2000&pages=1293&pmid=10837022&)]
- [33]Moulin, K., Truel, N., André, M., Arnauld, E., Nibbelink, M., Cousin, B., Dani, C., Pénicaud, L. & Casteilla, L. (2001) Biochem. J. 356**,** 659–664. [[DOI](https://doi.org/10.1042/0264-6021:3560659)] [[PMC free article](/articles/PMC1221881/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/11368797/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Biochem.%20J.&volume=356&publication_year=2001&pages=659&pmid=11368797&doi=10.1042/0264-6021:3560659&)] · DOI
Cited by
Sorted by citations
Adipocyte differentiation from the inside out
Rosen, E. D., & MacDougald, O. A. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2066 · Cited by 2,607 · 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
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
Adipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170 · see citing works
Transcriptional control of adipocyte formation
Farmer, S. R. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.07.001 · Cited by 1,836 · 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
Petrovic, N., Walden, T. B., Shabalina, I. G., Timmons, J. A., Cannon, B., & Nedergaard, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.053942 · Cited by 1,263 · see citing works
Self-citationPrdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice
Seale, P., Conroe, H. M., Estall, J. L., Kajimura, S., Frontini, A., Ishibashi, J., Cohen, P., Cinti, S., & Spiegelman, B. M. (2010) · Journal of Clinical Investigation · doi:10.1172/jci44271 · Cited by 1,241 · see citing works
Self-citationAdipose 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
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
Transcriptional Regulation of Metabolism
Desvergne, B., Michalik, L., & Wahli, W. (2006) · Physiological Reviews · doi:10.1152/physrev.00025.2005 · Cited by 889 · see citing works
New developments in adipogenesis
Lefterova, M. I., & Lazar, M. A. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2008.11.005 · Cited by 861 · 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
PPARγ agonists Induce a White-to-Brown Fat Conversion through Stabilization of PRDM16 Protein
Ohno, H., Shinoda, K., Spiegelman, B. M., & Kajimura, S. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.019 · Cited by 749 · see citing works
Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance
Fang, S., Suh, J. M., Reilly, S. M., Yu, E., Osborn, O., Lackey, D., Yoshihara, E., Perino, A., Jacinto, S., Lukasheva, Y., et al. (2015) · Nature Medicine · doi:10.1038/nm.3760 · Cited by 738 · 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-citationInitiation of myoblast to brown fat switch by a PRDM16–C/EBP-β transcriptional complex
Kajimura, S., Seale, P., Kubota, K., Lunsford, E., Frangioni, J. V., Gygi, S. P., & Spiegelman, B. M. (2009) · Nature · doi:10.1038/nature08262 · Cited by 703 · see citing works
Ali, A. T., Hochfeld, W. E., Myburgh, R., & Pepper, M. S. (2013) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2013.06.001 · Cited by 631 · 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
Adipose-Specific Knockout of raptor Results in Lean Mice with Enhanced Mitochondrial Respiration
Polak, P., Cybulski, N., Feige, J. N., Auwerx, J., Rüegg, M. A., & Hall, M. N. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.09.003 · Cited by 480 · see citing works
Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex
Kajimura, S., Seale, P., Tomaru, T., Erdjument-Bromage, H., Cooper, M. P., Ruas, J. L., Chin, S., Tempst, P., Lazar, M. A., & Spiegelman, B. M. (2008) · Genes & Development · doi:10.1101/gad.1666108 · Cited by 468 · see citing works
Kajimura, S., & Saito, M. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170252 · Cited by 428 · see citing works
Transcriptional Control of Brown Fat Development
Kajimura, S., Seale, P., & Spiegelman, B. M. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.03.005 · Cited by 417 · see citing works
Cao, L., Choi, E., Liu, X., Martin, A. S., Wang, C., Xu, X., & During, M. J. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.06.020 · Cited by 380 · see citing works
Brown fat as a therapy for obesity and diabetes
Cypess, A. M., & Kahn, C. R. (2010) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0b013e328337a81f · Cited by 376 · see citing works
Cinti, S. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.009662 · Cited by 350 · see citing works
Self-citationTailoring to RB: tumour suppressor status and therapeutic response
Knudsen, E. S., & Knudsen, K. E. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2401 · Cited by 345 · see citing works
Transcriptional 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 341 · see citing works
Transcriptional coregulators in the control of energy homeostasis
Feige, J. N., & Auwerx, J. (2007) · Trends in Cell Biology · doi:10.1016/j.tcb.2007.04.001 · Cited by 325 · see citing works
Rb regulates fate choice and lineage commitment in vivo
Calo, E., Quintero-Estades, J. A., Danielian, P. S., Nedelcu, S., Berman, S. D., & Lees, J. A. (2010) · Nature · doi:10.1038/nature09264 · Cited by 313 · 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
Role of A-type lamins in signaling, transcription, and chromatin organization
Andrés, V., & González, J. M. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200904124 · Cited by 289 · see citing works
Development of insulin resistance in mice lacking PGC-1α in adipose tissues
Kleiner, S., Mepani, R. J., Laznik, D., Li, Y., Jurczak, M. J., Jornayvaz, F. R., Estall, J. L., Bhowmick, D. C., Shulman, G. I., & Spiegelman, B. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207287109 · Cited by 286 · see citing works
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 276 · see citing works
Hedgehog signaling plays a conserved role in inhibiting fat formation
Suh, J. M., Gao, X., McKay, J., McKay, R. M., Salo, Z., & Graff, J. M. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2005.11.012 · Cited by 271 · see citing works
Subcutaneous fat in normal and diseased states
Avram, M. M., Avram, A. S., & James, W. D. (2007) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2006.06.022 · Cited by 266 · see citing works
Chen, B. J., Mariño‐Enríquez, A., Fletcher, C. D. �., & Hornick, J. L. (2012) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e31825d532d · Cited by 254 · see citing works
Remodeling of White Adipose Tissue after Retinoic Acid Administration in Mice
Mercader, J., Ribot, J., Murano, I., Felipe, F., Cinti, S., Bonet, M. L., & Palou, A. (2006) · Endocrinology · doi:10.1210/en.2006-0760 · Cited by 244 · see citing works
Self-citationBrown fat biology and thermogenesis
Richard, D. (2010) · Frontiers in bioscience · doi:10.2741/3786 · Cited by 247 · see citing works
Molecular Mechanisms of Adipogenesis: The Anti-adipogenic Role of AMP-Activated Protein Kinase
Ahmad, B., Serpell, C. J., Fong, I. L., & Wong, E. H. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00076 · Cited by 253 · see citing works
Cantor, S., Drapkin, R., Zhang, F., Lin, Y., Han, J., Pamidi, S., & Livingston, D. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308717101 · Cited by 240 · see citing works
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 231 · see citing works
Lipid metabolism in mammalian tissues and its control by retinoic acid
Bonet, M. L., Ribot, J., & Palou, A. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.06.001 · Cited by 212 · see citing works
Berry, D. C., Jiang, Y., Arpke, R. W., Close, E. L., Uchida, A., Reading, D., Berglund, E. D., Kyba, M., & Graff, J. M. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.10.023 · Cited by 214 · see citing works
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 · see citing works
Giralt, A., Hondares, E., Villena, J. A., Ribas, F., Díaz-Delfín, J., Giralt, M., Iglesias, R., & Villarroya, F. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.202390 · Cited by 210 · see citing works
E2F1, a Novel Regulator of Metabolism
Denechaud, P., Fajas, L., & Giralt, A. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00311 · Cited by 207 · see citing works
A-type lamins: Guardians of the soma?
Hutchison, C., & Worman, H. J. (2004) · Nature Cell Biology · doi:10.1038/ncb1104-1062 · Cited by 208 · see citing works
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 195 · see citing works
Self-citationScimè, A., Grenier, G., Huh, M. S., Gillespie, M. A., Bevilacqua, L., Harper, M.-E., & Rudnicki, M. A. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.10.002 · Cited by 199 · see citing works
UCP1: its involvement and utility in obesity
Kozak, L. P., & Anunciado‐Koza, R. P. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.236 · Cited by 200 · 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
Fat-specific Protein 27 Regulates Storage of Triacylglycerol
Keller, P., Petrie, J. T., Rose, P. D., Gerin, I., Hahn, W. S., Chiang, S.-H., Nielsen, A. R., Fischer, C. P., Pedersen, B. K., & MacDougald, O. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708323200 · Cited by 187 · see citing works
The adipose organ: white‐brown adipocyte plasticity and metabolic inflammation
Smorlesi, A., Frontini, A., Giordano, A., & Cinti, S. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01039.x · Cited by 163 · see citing works
Self-citationRIP140-Targeted Repression of Gene Expression in Adipocytes
Christian, M., Kiskinis, E., Debevec, D., Leonardsson, G., White, R., & Parker, M. G. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9383-9391.2005 · Cited by 181 · see citing works
Collins, S., Cao, W., & Robidoux, J. (2004) · Molecular Endocrinology · doi:10.1210/me.2004-0193 · Cited by 179 · see citing works
Xue, B., Coulter, A. A., Rim, J. S., Koza, R. A., & Kozak, L. P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.18.8311-8322.2005 · Cited by 179 · see citing works
Dorner, D., Vlcek, S., Foeger, N., Gajewski, A., Makolm, C., Gotzmann, J., Hutchison, C. J., & Foisner, R. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200511149 · Cited by 179 · see citing works
Regulatory circuits controlling white versus brown adipocyte differentiation
Hansen, J. B., & Kristiansen, K. (2006) · Biochemical Journal · doi:10.1042/bj20060402 · Cited by 178 · see citing works
Self-citationTownsend, K. L., & Tseng, Y. (2012) · Adipocyte · doi:10.4161/adip.18951 · Cited by 172 · see citing works
Subcutaneous fat in normal and diseased states
Avram, A. S., Avram, M. M., & James, W. D. (2005) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2005.05.015 · Cited by 169 · see citing works
Lengthened G1 Phase Indicates Differentiation Status in Human Embryonic Stem Cells
Calder, A. N., Roth-Albin, I., Bhatia, S., Pilquil, C., Lee, J., Bhatia, M., Levadoux‐Martin, M., McNicol, J. D., Russell, J., Collins, T., et al. (2012) · Stem Cells and Development · doi:10.1089/scd.2012.0168 · Cited by 160 · see citing works
The retinoblastoma tumor-suppressor gene, the exception that proves the rule
Goodrich, D. W. (2006) · Oncogene · doi:10.1038/sj.onc.1209616 · Cited by 166 · see citing works
Adipose Organ Development and Remodeling
Cinti, S. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170042 · Cited by 187 · see citing works
Self-citationFree radicals and male reproduction.
Agarwal, A. K., & Allamaneni, S. S. R. (2011) · PubMed · Cited by 154 · see citing works
A Genome Scan for Positive Selection in Thoroughbred Horses
Gu, J., Orr, N., Park, S. D., Katz, L. M., Сулимова, Г. Е., MacHugh, D. E., & Hill, E. W. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005767 · Cited by 157 · see citing works
Emerging role of bone morphogenetic proteins in adipogenesis and energy metabolism
Schulz, T. J., & Tseng, Y.-H. (2009) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2009.10.019 · Cited by 154 · see citing works
Zhang, X., Zhang, Q.-X., Wang, X., Zhang, L., Qu, W., Bao, B., Liu, C.-A., & Liu, J. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.108 · Cited by 140 · see citing works
Effects of Wnt Signaling on Brown Adipocyte Differentiation and Metabolism Mediated by PGC-1α
Kang, S., Bajnok, L., Longo, K. A., Petersen, R. K., Hansen, J. B., Kristiansen, K., & MacDougald, O. A. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.4.1272-1282.2005 · Cited by 135 · see citing works
Self-citationAblation of LGR4 promotes energy expenditure by driving white-to-brown fat switch
Wang, J., Liu, R., Wang, F., Hong, J., Li, X., Chen, M., Ke, Y., Zhang, X., Ma, Q., Wang, R., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2867 · Cited by 136 · see citing works
RB, the conductor that orchestrates life, death and differentiation
Khidr, L., & Chen, P.-L. (2006) · Oncogene · doi:10.1038/sj.onc.1209612 · Cited by 123 · see citing works
The retinoblastoma tumor suppressor and stem cell biologyPreprint
Sage, J. (2012) · Genes & Development · doi:10.1101/gad.193730.112 · Cited by 119 · see citing works
Dali‐Youcef, N., Mataki, C., Coste, A., Messaddeq, N., Giroud, S., Blanc, S., Koehl, C., Champy, M., Chambon, P., Lluis Fajas, A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611568104 · Cited by 115 · see citing works
Developmental and functional heterogeneity of white adipocytes within a single fat depot
Lee, K. Y., Luong, Q., Sharma, R., Dreyfuss, J., Ussar, S., & Kahn, C. R. (2018) · EMBO Journal · doi:10.15252/embj.201899291 · Cited by 95 · see citing works
Rahman, S. M., Janssen, R. C., Choudhury, M., Baquero, K. C., Aikens, R. M., de la Houssaye, B. A., & Friedman, J. E. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.410613 · Cited by 114 · see citing works
Fatty acids and expression of adipokines
Drevon, C. A. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.11.019 · Cited by 113 · see citing works
Gotzmann, J., & Foisner, R. (2005) · Histochemistry and Cell Biology · doi:10.1007/s00418-005-0050-8 · Cited by 109 · see citing works
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 108 · see citing works
Anunciado‐Koza, R. P., Ukropec, J., Koza, R. A., & Kozak, L. P. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804268200 · Cited by 108 · see citing works
Retinoblastoma Tumor Suppressor: Where Cancer Meets the Cell Cycle
Knudsen, E. S., & Knudsen, K. E. (2006) · Experimental Biology and Medicine · doi:10.1177/153537020623100713 · Cited by 105 · see citing works
Egerod, K. L., Holst, B., Petersen, P. S., Hansen, J. B., Mulder, J., Hökfelt, T. G. M., & Schwartz, T. W. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0055 · Cited by 101 · see citing works
Self-citationEmerging roles of RETINOBLASTOMA-RELATED proteins in evolution and plant development
Gutzat, R., Borghi, L., & Gruissem, W. (2012) · Trends in Plant Science · doi:10.1016/j.tplants.2011.12.001 · Cited by 98 · see citing works
Aguilar, V. M., & Fajas, L. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000089 · Cited by 100 · see citing works
Mercader, J., Palou, A., & Bonet, M. L. (2010) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2010.07.007 · Cited by 95 · see citing works
Hormone‐sensitive lipase (HSL) is also a retinyl ester hydrolase: evidence from mice lacking HSL
Ström, K., Gundersen, T. E., Hansson, O., Lucas, S., Fernandez, C., Blomhoff, R., & Holm, C. (2009) · The FASEB Journal · doi:10.1096/fj.08-120923 · Cited by 89 · see citing works
Reversible physiological transdifferentiation in the adipose organ
Cinti, S. (2009) · Proceedings of The Nutrition Society · doi:10.1017/s0029665109990140 · Cited by 88 · see citing works
Self-citationThe tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting
Elattar, S., Dimri, M., & Ande, S. (2018) · The FASEB Journal · doi:10.1096/fj.201701465rr · Cited by 88 · see citing works
Metabolic regulation and the anti-obesity perspectives of human brown fat
Scheele, C. C., & Nielsen, S. J. (2017) · Redox Biology · doi:10.1016/j.redox.2017.04.011 · Cited by 86 · see citing works
Nicolay, B., Danielian, P. S., Kottakis, F., Lapek, J. D., Sanidas, I., Miles, W. O., Dehnad, M., Tschöp, K., Gierut, J. J., Manning, A. L., et al. (2015) · Genes & Development · doi:10.1101/gad.264127.115 · Cited by 84 · see citing works
Glucocorticoid Receptor Accelerates, but Is Dispensable for, Adipogenesis
Park, Y.-K., & Ge, K. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.00260-16 · Cited by 84 · see citing works
All-Trans Retinoic Acid Increases Oxidative Metabolism in Mature Adipocytes
Mercader, J., Madsen, L., Felipe, F., Palou, A., Kristiansen, K., & Bonet, M. L. (2007) · Cellular Physiology and Biochemistry · doi:10.1159/000110717 · Cited by 84 · see citing works
Self-citationVáraljai, R., Islam, A. B. M. M. K., Beshiri, M. L., Rehman, J., López-Bigas, N., & Benevolenskaya, E. V. (2015) · Genes & Development · doi:10.1101/gad.264036.115 · Cited by 82 · see citing works
Auffret, J., Viengchareun, S., Carré, N., Denis, R., Magnan, C., Marie, P., Muscat, A., Fève, B., Lombès, M., & Binart, N. (2012) · The FASEB Journal · doi:10.1096/fj.12-204958 · Cited by 79 · see citing works
Xie, X., Yu, H., Wang, Y., Zhou, Y., Li, G., Ruan, Z., Li, F., Wang, X., Liu, H., & Zhang, J. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.08.017 · Cited by 77 · see citing works
CDK6 inhibits white to beige fat transition by suppressing RUNX1
Hou, X. S., Zhang, Y., Li, W., Hu, A. J., Luo, C., Zhou, W., Hu, J. K., Daniele, S. G., Wang, J., Sheng, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03451-1 · Cited by 76 · see citing works
Liu, P., Huang, S., Ling, S., Xu, S., Wang, F., Zhang, W., Zhou, R., He, L., Xia, X., Yao, Z., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12988-8 · Cited by 76 · see citing works
The multiple connections between pRB and cell metabolism
Nicolay, B., & Dyson, N. J. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2013.07.012 · Cited by 76 · see citing works
Adipose tissue-derived cells: from physiology to regenerative medicine
Casteilla, L., & Dani, C. (2006) · Diabetes & Metabolism · doi:10.1016/s1262-3636(07)70297-5 · Cited by 75 · see citing works
Lipodystrophy in HIV 1-infected patients: lessons for obesity research
Villarroya, F., Domingo, P., & Giralt, M. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803698 · Cited by 74 · see citing works
Burgos, P. V., Klattenhoff, C., de la Fuente-Ortega, E., Rigotti, A., & González, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400295101 · Cited by 73 · see citing works
- Authors
- Hansen, J. B., Jørgensen, C., Petersen, R. K., Hallenborg, P., De Matteis, R., Bøye, H. A., Petrovic, N., Enerbäck, S., Nedergaard, J., Cinti, S., Riele, H. T., & Kristiansen, K.
- Affiliations
- Stockholm University (SE)
- Departments of Biochemistry and Molecular Biology and Anatomy and Neurobiology, University of Southern Denmark, DK-5230 Odense M, Denmark; The Netherlands Cancer Institute, Division of Molecular Biology, NL-1066 CX Amsterdam, The Netherlands; Institute of Normal Human Morphology, Faculty of Medicine, University of Ancona, Ancona 60020, Italy; The Wenner-Gren Institute, Stockholm University, SE-10691 Stockholm, Sweden; and Medical Genetics, Department of Medical Biochemistry, Göteborg University, SE...
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-03-15
- Volume
- 101
- Issue
- 12
- Pages
- 4112-4117
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC384703
- OpenAlex
- W2145157621
- Cited by
- 287
- References
- 36
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 15 · 2017: 12 · 2016: 11 · 2015: 14 · 2014: 16 · 2013: 23 · 2012: 23
- FWCI
- 12.76
- Type
- journal article
- Language
- en
- Update notices
- correction (2004-04-27)
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- 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
- retinoblastoma protein, white adipocyte differentiation, brown adipocyte differentiation, UCP1, FOXC2, protein kinase A, protein phosphorylation, beta3-adrenergic agonists, adipocyte transdifferentiation, adipose tissue
- MeSH terms
- Uncoupling Protein 1, Cyclic AMP, Animals, Antigens, Polyomavirus Transforming, Adipose Tissue, Brown, Carrier Proteins, Cell Differentiation, Fibroblasts, Ion Channels, Membrane Proteins, Mice, Inbred C57BL, Simian virus 40, Retinoblastoma Protein, Rats, Sprague-Dawley, Adipocytes, Mitochondrial Proteins, Mice, Rats
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