p38 Mitogen-Activated Protein Kinase Is the Central Regulator of Cyclic AMP-Dependent Transcription of the Brown Fat Uncoupling Protein 1 Gene
Open accessAbstract
It is well established that catecholamine-stimulated thermogenesis in brown fat requires beta-adrenergic elevations in cyclic AMP (cAMP) to increase expression of the uncoupling protein 1 (UCP1) gene. However, little is known about the downstream components of the signaling cascade or the relevant transcription factor targets thereof. Here we demonstrate that cAMP- and protein kinase A-dependent activation of p38 mitogen-activated protein kinase (MAPK) in brown adipocytes is an indispensable step in the transcription of the UCP1 gene in mice. By phosphorylating activating transcription factor 2 (ATF-2) and peroxisome proliferator-activated receptor gamma (PPARgamma) coativator 1alpha (PGC-1alpha), members of two distinct nuclear factor families, p38 MAPK controls the expression of the UCP1 gene through their respective interactions with a cAMP response element and a PPAR response element that both reside within a critical enhancer motif of the UCP1 gene. Activation of ATF-2 by p38 MAPK additionally serves as the cAMP sensor that increases expression of the PGC-1alpha gene itself in brown adipose tissue. In conclusion, our findings illustrate that by orchestrating the activity of multiple transcription factors, p38 MAPK is a central mediator of the cAMP signaling mechanism of brown fat that promotes thermogenesis.
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Cold induces Ucp1 expression in both humans and rodents, essentially by activating β-adrenergic receptors and the cAMP-dependent PKA signaling pathway.
“The most well-known condition to induce Ucp1 expression in both humans and rodents is cold, essentially by activating β-adrenergic receptors and the cAMP-dependent protein kinase (PKA)-dependent signaling pathway [38,39].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [39]
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Cites
Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose.
Thomas, P. S. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.9.5201 · Cited by 7,937 · see citing works
Mitogen-Activated Protein Kinase Pathways Mediated by ERK, JNK, and p38 Protein Kinases
Johnson, G. L., & Lapadat, R. (2002) · Science · doi:10.1126/science.1072682 · Cited by 4,295 · see citing works
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
Self-citationLehmann, J. M., Moore, L. B., Smith-Oliver, T. A., Wilkison, W. O., Willson, T. M., & Kliewer, S. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.22.12953 · Cited by 3,626 · see citing works
Puigserver, P., & Spiegelman, B. M. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0012 · Cited by 2,076 · see citing works
Self-citationEpac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP
de Rooij, J., Zwartkruis, F. J. T., Verheijen, M. H. G., Cool, R. H., Nijman, S. M. B., Wittinghofer, A., & Bos, J. L. (1998) · Nature · doi:10.1038/24884 · Cited by 1,970 · see citing works
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
Yoon, J. C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C. R., Granner, D. K., et al. (2001) · Nature · doi:10.1038/35093050 · Cited by 1,821 · see citing works
Self-citationTowards 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
Self-citationThe p38 signal transduction pathway Activation and function
Ono, K., & Han, J. (2000) · Cellular Signalling · doi:10.1016/s0898-6568(99)00071-6 · Cited by 1,571 · see citing works
Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms
Dérijard, B., Raingeaud, J., Barrett, T., Wu, I.-H., Han, J., Ulevitch, R. J., & Davis, R. J. (1995) · Science · doi:10.1126/science.7839144 · Cited by 1,555 · 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
Self-citationJi, T. H., Grossmann, M., & Ji, I. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.28.17299 · Cited by 1,291 · see citing works
Lefkowitz, R. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.30.18677 · Cited by 1,067 · see citing works
Coactivator and corepressor complexes in nuclear receptor function
Xu, L., Glass, C. K., & Rosenfeld, M. G. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)80021-5 · Cited by 897 · see citing works
The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP
Ricquier, D., & Bouillaud, F. (2000) · Biochemical Journal · doi:10.1042/bj3450161 · Cited by 806 · see citing works
Cytokine Stimulation of Energy Expenditure through p38 MAP Kinase Activation of PPARγ Coactivator-1
Puigserver, P., Rhee, J., Lin, J., Wu, Z., Yoon, J. C., Zhang, C.-Y., Krauss, S., Mootha, V. K., Lowell, B. B., & Spiegelman, B. M. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00390-2 · Cited by 732 · cited 4× · see citing works
“Importantly, under these same conditions, a PGC-1 construct (PGC-1A3) in which the p38 MAPK phosphorylation sites were mutated (T262A, S265A, and T298A) ( 31 ) was completely unable to promote transcription of the UCP1 enhancer under either basal or stimulated conditions (Fig. 4C).”
BackgroundMethodInfluentialSelf-citationFat cell adrenergic receptors and the control of white and brown fat cell function
Lafontan, M., & Berlan, M. (1993) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37695-1 · Cited by 636 · see citing works
Nedergaard, J., Golozoubova, V., Matthias, A., Asadi, A., Jacobsson, A., & Cannon, B. (2001) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(00)00247-4 · Cited by 615 · see citing works
Activation of PPARγ Coactivator-1 Through Transcription Factor Docking
Puigserver, P., Adelmant, G., Wu, Z., Fan, M., Xu, J., O’Malley, B. W., & Spiegelman, B. M. (1999) · Science · doi:10.1126/science.286.5443.1368 · Cited by 596 · see citing works
Self-citationBadger, A. M., Bradbeer, J. N., Votta, B. J., Lee, J. C., Adams, J. L., & Griswold, D. E. (1996) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)21307-6 · Cited by 499 · see citing works
Acquirement 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 · cited 1× · see citing works
“Recently, it has been shown that overexpression of the PGC-1 gene can promote the occurrence of brown fat features in human white adipocytes (39).”
BackgroundThe Primary Structure of p38γ: A New Member of p38 Group of MAP Kinases
Li, Z., Jiang, Y., Ulevitch, R. J., & Han, J. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1662 · Cited by 390 · see citing works
Aquila, H., Link, T. A., & Klingenberg, M. (1985) · The EMBO Journal · doi:10.1002/j.1460-2075.1985.tb03941.x · Cited by 368 · see citing works
β-Adrenergic Activation of p38 MAP Kinase in Adipocytes
Cao, W., Medvedev, A. V., Daniel, K. W., & Collins, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101049200 · Cited by 327 · see citing works
Self-citationJacobsson, A., Stadler, U., Glotzer, M. A., & Kozak, L. P. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36228-2 · Cited by 300 · see citing works
Underwood, D. C., Osborn, R. R., Bochnowicz, S., Webb, E. F., Rieman, D. J., Lee, J. C., Romanic, A. M., Adams, J. L., Hay, D. W. P., & Griswold, D. E. (2000) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.2000.279.5.l895 · Cited by 297 · see citing works
Sears, I. B., MacGinnitie, M. A., Kovács, L., & Graves, R. A. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.7.3410 · Cited by 270 · see citing works
Collins, S., Caron, M. G., & Lefkowitz, R. J. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)76507-7 · Cited by 261 · see citing works
Self-citationUnderwood, D. C., Osborn, R. R., Kotzer, C. J., Adams, J. L., Lee, J. C., Webb, E. F., Carpenter, D. C., Bochnowicz, S., Thomas, H. C., Hay, D. W. P., et al. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39230-4 · Cited by 241 · see citing works
Collins, S., Daniel, K. W., Rohlfs, E. M., Ramkumar, V., Taylor, I. L., & Gettys, T. W. (1994) · Molecular Endocrinology · doi:10.1210/mend.8.4.7914350 · Cited by 221 · see citing works
Self-citationDalgaard, L. T., & Pedersen, O. B. (2001) · Diabetologia · doi:10.1007/s001250100596 · Cited by 217 · see citing works
Regulation of the uncoupling protein gene expression
Silva, J. E., & Rabelo, R. (1997) · European Journal of Endocrinology · doi:10.1530/eje.0.1360251 · Cited by 204 · see citing works
Kozak, U. C., Kopecký, J., Teisinger, J., Enerbäck, S., Boyer, B. B., & Kozak, L. P. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.1.59 · Cited by 173 · see citing works
Collins, S., Altschmied, J., Herbsman, O., Caron, M. G., Mellon, P. L., & Lefkowitz, R. J. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30662-2 · Cited by 135 · see citing works
Self-citationBukowiecki, L. J., Géloën, A., & Collet, A. (1986) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1986.250.6.c880 · Cited by 135 · see citing works
The mitochondrial uncoupling protein gene. Correlation of exon structure to transmembrane domains.
Kozak, L. P., Britton, J. H., Kozak, U. C., & Wells, J. M. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)37751-2 · Cited by 121 · 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
Self-citationCassard, A., Gelly, C., Fox, N. W., Schrementi, J. P., Raimbault, S., Klaus, S., Forest, C. D., Bouillaud, F., & Ricquier, D. (1993) · Molecular Endocrinology · doi:10.1210/mend.7.4.8388995 · Cited by 113 · see citing works
Transcriptional Regulation of the Mouse Uncoupling Protein-2 Gene
Medvedev, A. V., Snedden, S. K., Raimbault, S., Ricquier, D., & Collins, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010587200 · Cited by 104 · see citing works
Self-citationGenetic and physiological analysis of the role of uncoupling proteins in human energy homeostasis
Pecqueur, C., Couplan, E., Bouillaud, F., & Ricquier, D. (2000) · Journal of Molecular Medicine · doi:10.1007/s001090000150 · Cited by 85 · see citing works
Yubero, P., Barberá, M., Alvarez, R., Viñas, O., Mampel, T., Iglesias, R., Villarroya, F., & Giralt, M. (1998) · Molecular Endocrinology · doi:10.1210/mend.12.7.0137 · Cited by 63 · see citing works
Cassard, A., Gelly, C., Bouillaud, F., & Ricquier, D. (1998) · Biochemical Journal · doi:10.1042/bj3330243 · Cited by 48 · see citing works
Joyeux‐Faure, M., Boumendjel, A., Carroll, R., Ribuot, C., Godin‐Ribuot, D., & Yellon, D. M. (2000) · Cardiovascular Drugs and Therapy · doi:10.1023/a:1007847111368 · Cited by 22 · see citing works
Nucleotide sequence of the humanβ-actin promoter 5′ flanking region
Miyamoto, N. G. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.21.9095 · Cited by 14 · see citing works
Luttrell, L. M. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00551-8 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [14]Jacobsson, A., U. Stadler, M. A. Glotzer, and L. P. Kozak. 1985. Mitochondrial uncoupling protein from mouse brown fat. J. Biol. Chem. 260:16250-16254. [PubMed] [Google Scholar]
- [17]Kozak, L., J. Britton, U. Kozak, and J. Wells. 1988. The mitochondrial uncoupling protein gene. J. Biol. Chem. 263:12274-12277. [PubMed] [Google Scholar]
- [21]Lehmann, J. M., L. B. Moore, T. A. Smith-Oliver, W. O. Wilkison, T. M. Willson, and S. A. Kliewer. 1995. An antidiabetic thiazolidinedione is a high affinity ligand for the nuclear receptor PPARγ. J. Biol. Chem. 270:12953-12956. [DOI] [PubMed] [Google Scholar]
Cited by
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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
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Lin, J., Handschin, C., & Spiegelman, B. M. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.004 · Cited by 2,130 · see citing works
“Stimulation of activating transcription factor 2 (ATF2) by p38 MAP kinase has also been shown to modulate the induction of PGC1α in brown fat by cold (Cao et al., 2004).”
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Tontonoz, P., & Spiegelman, B. M. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061307.091829 · Cited by 2,085 · see citing works
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Self-citationBordicchia, M., Liu, D., Amri, E.-Z., Ailhaud, G., Dessì-Fulgheri, P., Zhang, C., Takahashi, N., Sarzani, R., & Collins, S. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59701 · Cited by 872 · see citing works
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Akimoto, T., Pohnert, S. C., Li, P., Zhang, M., Gumbs, C., Rosenberg, P. B., Williams, R. S., & Yan, Z. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m408862200 · Cited by 714 · see citing works
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Yan, Z., Okutsu, M., Akhtar, Y., & Lira, V. A. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00993.2010 · Cited by 338 · see citing works
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β-adrenoceptor signaling networks in adipocytes for recruiting stored fat and energy expenditure
Collins, S. (2011) · Frontiers in Endocrinology · doi:10.3389/fendo.2011.00102 · Cited by 230 · see citing works
Self-citationInsulin Resistance and Diabetes Mellitus in Alzheimer’s Disease
Burillo, J., Marqués, P., Jiménez, B., González-Blanco, C., Benito, M., & Guillén, C. (2021) · Cells · doi:10.3390/cells10051236 · Cited by 234 · see citing works
Effects of Resveratrol and SIRT1 on PGC-1α Activity and Mitochondrial Biogenesis: A Reevaluation
Higashida, K., Kim, S. H., Jung, S. R., Asaka, M., Holloszy, J. O., & Han, D.-H. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001603 · Cited by 228 · see citing works
Machado, S. A., Pasquarelli-do-Nascimento, G., da Silva, D. S., Farias, G. R., Santos, I. D. O., Baptista, L. B., & Magalhães, K. G. (2022) · Nutrition & Metabolism · doi:10.1186/s12986-022-00694-0 · Cited by 229 · see citing works
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 215 · see citing works
Celis, J. E., Moreira, J. M. A., Cabezón, T., Gromov, P., Friis, E., Rank, F. E., & Gromova, I. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500030-mcp200 · Cited by 216 · 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
PPARs in the Control of Uncoupling Proteins Gene Expression
Villarroya, F., Iglesias, R., & Giralt, M. (2007) · PPAR Research · doi:10.1155/2007/74364 · Cited by 207 · see citing works
Obesity I: Overview and molecular and biochemical mechanisms
Lustig, R. H., Collier, D., Kassotis, C., Roepke, T. A., Kim, M. J., Blanc, E., Barouki, R., Bansal, A., Cave, M. C., Chatterjee, S., et al. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115012 · Cited by 203 · see citing works
Regulation by exercise of skeletal muscle content of mitochondria and GLUT4.
Holloszy, J. O. (2008) · PubMed · Cited by 202 · 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
Vernochet, C., Peres, S. B., Davis, K. E., McDonald, M. E., Qiang, L., Wang, H., Scherer, P. E., & Farmer, S. R. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01899-08 · Cited by 199 · see citing works
Activation of mTORC1 is essential for β-adrenergic stimulation of adipose browning
Liu, D., Bordicchia, M., Zhang, C., Fang, H., Wei, W., Li, J., Guilherme, A., Guntur, K., Czech, M., & Collins, S. (2016) · Journal of Clinical Investigation · doi:10.1172/jci83532 · Cited by 194 · see citing works
Self-citationHuman adipose beiging in response to cold and mirabegron
Finlin, B. S., Memetimin, H., Confides, A. L., Kasza, I., Zhu, B., Vekaria, H. J., Harfmann, B. D., Jones, K. A., Johnson, Z., Westgate, P. M., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.121510 · Cited by 194 · see citing works
IL-27 signalling promotes adipocyte thermogenesis and energy expenditure
Wang, Q., Li, D., Cao, G., Shi, Q., Zhu, J., Zhang, M., Cheng, H., Wen, Q., Xu, H. Y., Zhu, L., et al. (2021) · Nature · doi:10.1038/s41586-021-04127-5 · Cited by 187 · see citing works
Adipose Tissue and Metabolic Health
An, S.-M., Cho, S.-H., & Yoon, J. C. (2023) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2023.0011 · Cited by 184 · see citing works
Hondares, E., Mora, O., Yubero, P., de la Concepción, M. L. R., Iglesias, R., Giralt, M., & Villarroya, F. (2006) · Endocrinology · doi:10.1210/en.2006-0070 · Cited by 183 · see citing works
RIP140-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
Self-citationXue, 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
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
White-to-brown metabolic conversion of human adipocytes by JAK inhibition
Moisan, A., Lee, Y., Zhang, J. D., Hudak, C. S. S., Meyer, C. A., Prummer, M., Zoffmann, S., Truong, H., Ebeling, M., Kiialainen, A., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3075 · Cited by 177 · see citing works
Skeletal muscle “mitochondrial deficiency” does not mediate insulin resistance
Holloszy, J. O. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.26717c · Cited by 175 · see citing works
A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity
Chung, K.-J., Chatzigeorgiou, A., Economopoulou, M., Garcia-Martin, R., Alexaki, V. I., Mitroulis, I., Nati, M., Gebler, J., Ziemssen, T., Goelz, S. E., et al. (2017) · Nature Immunology · doi:10.1038/ni.3728 · Cited by 175 · see citing works
Townsend, K. L., & Tseng, Y. (2012) · Adipocyte · doi:10.4161/adip.18951 · Cited by 172 · see citing works
Exercise-induced hormesis and skeletal muscle health
Ji, L. L., Kang, C., & Zhang, Y. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.02.025 · Cited by 176 · see citing works
Schaiff, W. T., Bildirici, İ., Cheong, M., Chern, P. L., Nelson, D. M., & Sadovsky, Y. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-2265 · Cited by 173 · see citing works
Tsoli, M., Moore, M. M., Burg, D. W., Painter, A., Taylor, R., Lockie, S. H., Turner, N. A., Warren, A., Cooney, G., Oldfield, B. J., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3536 · Cited by 172 · see citing works
Qi, Y., Xu, Z., Zhu, Q., Thomas, C., Kumar, R., Feng, H., Dostal, D. E., White, M. F., Baker, K. M., & Guo, S. (2013) · Diabetes · doi:10.2337/db13-0095 · Cited by 167 · see citing works
Hallberg, M., Morganstein, D. L., Kiskinis, E., Shah, K., Kralli, A., Dilworth, S. M., White, R., Parker, M. G., & Christian, M. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00504-08 · Cited by 164 · see citing works
Adipose Organ Development and Remodeling
Cinti, S. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170042 · Cited by 187 · see citing works
Brown, Beige, and White: The New Color Code of Fat and Its Pharmacological Implications
Pfeifer, A., & Hoffmann, L. S. (2014) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010814-124346 · Cited by 163 · see citing works
Free radicals and male reproduction.
Agarwal, A. K., & Allamaneni, S. S. R. (2011) · PubMed · Cited by 154 · see citing works
Whitehead, A., Krause, F. N., Moran, A., MacCannell, A. D. V., Scragg, J. L., McNally, B. D., Boateng, E. A., Murfitt, S. A., Virtue, S., Wright, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22272-3 · Cited by 161 · see citing works
Apoptotic brown adipocytes enhance energy expenditure via extracellular inosine
Niemann, B., Haufs-Brusberg, S., Puetz, L., Feickert, M., Jaeckstein, M. Y., Hoffmann, A., Zurkovic, J., Heine, M., Trautmann, E.-M., Müller, C. E., et al. (2022) · Nature · doi:10.1038/s41586-022-05041-0 · Cited by 161 · see citing works
Brown and Beige Adipose Tissues in Health and Disease
Rui, L. (2017) · Comprehensive physiology · doi:10.1002/cphy.c170001 · Cited by 177 · see citing works
Han, J., Wu, J., & Silke, J. (2020) · F1000Research · doi:10.12688/f1000research.22092.1 · Cited by 159 · see citing works
Pearen, M. A., Myers, S., Raichur, S., Ryall, J. G., Lynch, G. S., & Muscat, G. E. O. (2008) · Endocrinology · doi:10.1210/en.2007-1202 · Cited by 156 · see citing works
Fu, W., Liu, Y., & Yin, H. (2019) · Stem Cells International · doi:10.1155/2019/9757201 · Cited by 159 · see citing works
Ligand‐directed signalling at β‐adrenoceptors
Evans, B. A., Sato, M., Sarwar, M., Hutchinson, D. S., & Summers, R. J. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00602.x · Cited by 153 · see citing works
Mitochondrial biogenesis and turnover
Diaz, F., & Moraes, C. T. (2008) · Cell Calcium · doi:10.1016/j.ceca.2007.12.004 · Cited by 151 · see citing works
MicroRNA‐455 regulates brown adipogenesis via a novel HIF1an‐AMPK‐PGC1α signaling network
Zhang, H., Guan, M., Townsend, K. L., Huang, T. L., An, D., Yan, X., Xue, R., Schulz, T. J., Winnay, J. N., Mori, M. A., et al. (2015) · EMBO Reports · doi:10.15252/embr.201540837 · Cited by 150 · see citing works
Alternative mRNA Splicing Produces a Novel Biologically Active Short Isoform of PGC-1α
Zhang, Y., Huypens, P., Adamson, A. W., Chang, J. S., Henagan, T. M., Boudreau, A., Lenard, N. R., Burk, D. H., Klein, J. C., Perwitz, N., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.037556 · Cited by 148 · see citing works
Mitochondria and PGC-1α in Aging and Age-Associated Diseases
Wenz, T. (2011) · Journal of Aging Research · doi:10.4061/2011/810619 · Cited by 149 · see citing works
Metabolic actions of natriuretic peptides and therapeutic potential in the metabolic syndrome
Schlueter, N., de Sterke, A., Willmes, D. M., Spranger, J., Jordan, J., & Birkenfeld, A. L. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.04.007 · Cited by 148 · see citing works
Mowers, J. C., Uhm, M., Reilly, S. M., Simon, J., Leto, D. E., Chiang, S.-H., Chang, L. C., & Saltiel, A. R. (2013) · eLife · doi:10.7554/elife.01119 · Cited by 149 · see citing works
Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat
Yao, L., Cui, X., Chen, Q., Yang, X., Fang, F., Zhang, J., Liu, G., Jin, W., & Chang, Y. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.06.069 · Cited by 144 · see citing works
p38 Mitogen-activated Protein Kinase Plays a Stimulatory Role in Hepatic Gluconeogenesis
Cao, W., Collins, Q. F., Becker, T. C., Robidoux, J., Lupo, E. G., Xiong, Y., Daniel, K. W., Floering, L. M., & Collins, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506223200 · Cited by 146 · see citing works
Self-citationHypertension Related to Obesity: Pathogenesis, Characteristics and Factors for Control
Meouchy, P., Wahoud, M., Allam, S., Chedid, R., Karam, W., & Karam, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012305 · Cited by 145 · see citing works
Transcriptional Regulatory Circuits Controlling Brown Fat Development and Activation
Seale, P. (2015) · Diabetes · doi:10.2337/db15-0203 · Cited by 143 · see citing works
Protein Kinase G Controls Brown Fat Cell Differentiation and Mitochondrial Biogenesis
Haas, B., Mayer, P. E., Jennissen, K., Scholz, D., Díaz, M. B., Bloch, W., Herzig, S., Fässler, R., & Pfeifer, A. (2009) · Science Signaling · doi:10.1126/scisignal.2000511 · Cited by 141 · see citing works
A heart–adipose tissue connection in the regulation of energy metabolism
Collins, S. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.234 · Cited by 138 · see citing works
Self-citationEffects 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
Crosstalk between mitochondrial (dys)function and mitochondrial abundance
Michel, S., Wanet, A., Pauw, A. D., Rommelaere, G., Arnould, T., & Renard, P. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.23021 · Cited by 132 · see citing works
Natriuretic peptides and cGMP signaling control of energy homeostasis
Moro, C., & Lafontan, M. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00704.2012 · Cited by 131 · see citing works
- Authors
- Cao, W., Daniel, K. W., Robidoux, J., Puigserver, P., Medvedev, A. V., Bai, X., Floering, L. M., Spiegelman, B. M., & Collins, S.
- Affiliations
- Duke University (US)
- Harvard University (US)
- Corresponding author
- Collins, Sheila
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-04-01
- Volume
- 24
- Issue
- 7
- Pages
- 3057-3067
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC371122
- OpenAlex
- W2162186867
- Cited by
- 605
- References
- 46
- Citations by year
- 2026: 17 · 2025: 33 · 2024: 36 · 2023: 29 · 2022: 28 · 2021: 46 · 2020: 51 · 2019: 28 · 2018: 29 · 2017: 29 · 2016: 37 · 2015: 27 · 2014: 26 · 2013: 34 · 2012: 26
- FWCI
- 10.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DK54477)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-54024, R01 DK54477, R01DK054024, R01DK053092, R01DK054477)
- Topics
- Health Sciences › Medicine › Physiology › 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 › Metabolism, Diabetes, and Cancer
- Keywords
- p38 MAPK, UCP1, brown adipocytes, thermogenesis, cAMP signaling, protein kinase A, ATF2, PGC-1α, PPAR response element, cAMP response element, enhancers, catecholamine signaling, beta-adrenergic signaling
- MeSH terms
- Uncoupling Protein 1, Cyclic AMP, Animals, Adipose Tissue, Brown, Carrier Proteins, Cells, Cultured, Cold Temperature, Enhancer Elements, Genetic, Enzyme Activation, Enzyme Inhibitors, Gene Expression Regulation, Humans, Ion Channels, Membrane Proteins, Mice, Inbred C57BL, Random Allocation, Transcription Factors, Transcription, Genetic, Uncoupling Agents, Signal Transduction, Adipocytes, Mitogen-Activated Protein Kinases, Thermogenesis, Mitochondrial Proteins, p38 Mitogen-Activated Protein Kinases, Mice
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