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HDAC11 suppresses the thermogenic program of adipose tissue via BRD2
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Abstract
Little is known about the biological function of histone deacetylase 11 (HDAC11), which is the lone class IV HDAC. Here, we demonstrate that deletion of HDAC11 in mice stimulates brown adipose tissue (BAT) formation and beiging of white adipose tissue (WAT). Consequently, HDAC11-deficient mice exhibit enhanced thermogenic potential and, in response to high-fat feeding, attenuated obesity, improved insulin sensitivity, and reduced hepatic steatosis. Ex vivo and cell-based assays revealed that HDAC11 catalytic activity suppresses the BAT transcriptional program, in both the basal state and in response to β-adrenergic receptor signaling, through a mechanism that is dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl-histone-binding protein. These findings define an epigenetic pathway for the regulation of energy homeostasis and suggest the potential for HDAC11-selective inhibitors for the treatment of obesity and diabetes.
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“These activities require the interaction of Hdac11 with the epigenetic reader BRD2 (Bagchi et al., 2018).”
From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Bagchi et al., 2018
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Citations
Cites
The metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function
Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481
IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040
Ogurtsova, K., Fernandes, J. D. D. R., Huang, Y., Linnenkamp, U., Guariguata, L., Cho, N. H., Cavan, D. A., Shaw, J. E., & Makaroff, L. (2017) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2017.03.024 · Cited by 7,138
Brown Adipose Tissue: Function and Physiological Significance
CANNON, B., & NEDERGAARD, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00015.2003 · Cited by 6,433
Prevalence of Obesity Among Adults and Youth: United States, 2015-2016.
Hales, C. M., Carroll, M. D., Fryar, C. D., & Ogden, C. L. (2017) · PubMed · Cited by 3,889
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
Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human
Wu, J., Boström, P., Sparks, L. M., Li, Y., Choi, J. H., Giang, A.-H., Khandekar, M. J., Virtanen, K. A., Nuutila, P., Schaart, G., et al. (2012) · Cell · doi:10.1016/j.cell.2012.05.016 · Cited by 3,406
A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes
Scherer, P. E., Williams, S. P., Fogliano, M., Baldini, G., & Lodish, H. F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.26746 · Cited by 3,238
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
What we talk about when we talk about fat
Rosen, E. D., & Spiegelman, B. M. (2014) · Cell · doi:10.1016/j.cell.2013.12.012 · Cited by 2,373
Mechanisms, Pathophysiology, and Management of Obesity
Heymsfield, S. B., & Wadden, T. A. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1514009 · Cited by 1,867
Gregoretti, I., Lee, Y.-M., & Goodson, H. V. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.02.006 · Cited by 1,456
NAD + in aging, metabolism, and neurodegeneration
Verdin, E. (2015) · Science · doi:10.1126/science.aac4854 · Cited by 1,319
Hill, J. O., Wyatt, H. R., & Peters, J. C. (2012) · Circulation · doi:10.1161/circulationaha.111.087213 · Cited by 1,317
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
Targeting the cancer epigenome for therapy
Jones, P. A., Issa, J. J., & Baylin, S. B. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.93 · Cited by 1,153
Class II Histone Deacetylases Act as Signal-Responsive Repressors of Cardiac Hypertrophy
Zhang, C. L., McKinsey, T. A., Chang, S., Antos, C. L., Hill, J. A., & Olson, E. N. (2002) · Cell · doi:10.1016/s0092-8674(02)00861-9 · Cited by 973
Mechanism of Fatty-Acid-Dependent UCP1 Uncoupling in Brown Fat Mitochondria
Fedorenko, A., Lishko, P. V., & Kirichok, Y. (2012) · Cell · doi:10.1016/j.cell.2012.09.010 · Cited by 968
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
Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression
Lagger, G., O'Carroll, D., Rembold, M., Khier, H., Tischler, J., Weitzer, G., Schuettengruber, B., Hauser, C., Brunmeir, R., Jenuwein, T., et al. (2002) · The EMBO Journal · doi:10.1093/emboj/21.11.2672 · Cited by 760
Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents
Mottamal, M., Zheng, S., Huang, T. L., & Wang, G. (2015) · Molecules · doi:10.3390/molecules20033898 · Cited by 698
Roberts, 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
Chang, S., McKinsey, T. A., Zhang, C. L., Richardson, J. A., Hill, J. A., & Olson, E. N. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.19.8467-8476.2004 · Cited by 612
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
Rahman, S., Sowa, M. E., Ottinger, M., Smith, J. A., Shi, Y., Harper, J. W., & Howley, P. M. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.01341-10 · Cited by 532
Galarraga, M., Campión, J., Muñoz‐Barrutia, A., Boqué, N., Moreno, H., Martínez, J. A., Milagro, F. I., & Ortíz-de-Solórzano, C. (2012) · Journal of Lipid Research · doi:10.1194/jlr.d023788 · Cited by 422
Maintenance of cardiac energy metabolism by histone deacetylase 3 in mice
Montgomery, R. L., Potthoff, M. J., Haberland, M., Qi, X., Matsuzaki, S., Humphries, K. M., Richardson, J. A., Bassel‐Duby, R., & Olson, E. N. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35847 · Cited by 365
Ishibashi, J., & Seale, P. (2010) · Science · doi:10.1126/science.1190816 · Cited by 356
Implications of nonshivering thermogenesis for energy balance regulation in humans
Lichtenbelt, W. D. V. M., & Schrauwen, P. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00652.2010 · Cited by 318
Hondares, E., Rosell, M., Díaz-Delfín, J., Olmos, Y., Monsalve, M., Iglesias, R., Villarroya, F., & Giralt, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.252775 · Cited by 302
The functional interactome landscape of the human histone deacetylase family
Joshi, P., Greco, T. M., Guise, A. J., Luo, Y., Yu, F., Nesvizhskii, A. I., & Cristea, I. M. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.26 · Cited by 289
Sirtuins in Epigenetic Regulation
Jing, H., & Lin, H. (2015) · Chemical Reviews · doi:10.1021/cr500457h · Cited by 276
Galmozzi, A., Mitro, N., Ferrari, A., Gers, E., Gilardi, F., Godio, C., Cermenati, G., Gualerzi, A., Donetti, E., Rotili, D., et al. (2012) · Diabetes · doi:10.2337/db12-0548 · Cited by 242
Zhao, Y., Londono, P., Cao, Y., Sharpe, E. J., Proenza, C., O’Rourke, R., Jones, K. L., Jeong, M. Y., Walker, L. A., Buttrick, P. M., et al. (2015) · Nature Communications · doi:10.1038/ncomms9243 · Cited by 232
Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge
Emmett, M. J., Lim, H., Jager, J., Richter, H. J., Adlanmérini, M., Peed, L. C., Briggs, E. R., Steger, D. J., Ma, T., Sims, C. A., et al. (2017) · Nature · doi:10.1038/nature22819 · Cited by 200
HDAC11 regulates type I interferon signaling through defatty-acylation of SHMT2
Cao, J., Sun, L., Aramsangtienchai, P., Spiegelman, N. A., Zhang, X., Huang, W., Seto, E., & Lin, H. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1815365116 · Cited by 189
Weyer, C., Tataranni, P. A., Snitker, S., Danforth, E., & Ravussin, E. (1998) · Diabetes · doi:10.2337/diabetes.47.10.1555 · Cited by 188
Brd2 disruption in mice causes severe obesity without Type 2 diabetes
Wang, F., Liu, H., Blanton, W. P., Belkina, A., Lebrasseur, N. K., & Denis, G. V. (2010) · Biochemical Journal · doi:10.1042/bj20090928 · Cited by 185
Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes
Lee, J., Takahashi, N., Yasubuchi, M., Kim, Y., Hashizaki, H., Kim, M., Sakamoto, T., Goto, T., & Kawada, T. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00010.2011 · Cited by 185
Larsen, T. M., Toubro, S., van Baak, M. A., Gottesdiener, K. M., Larson, P., Saris, W. H., & Astrup, A. (2002) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/76.4.780 · Cited by 179
Histone deacetylase 11 is a fatty-acid deacylase
Kutil, Z., Novakova, Z., Meleshin, M., Mikesova, J., Schutkowski, M., & Barinka, C. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.7b00942 · Cited by 174
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 168
Nicholls, D. G., BERNSON, V. S. M., & Heaton, G. M. (1978) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-0348-5559-4_9 · Cited by 160
Histone Deacetylase 9 Is a Negative Regulator of Adipogenic Differentiation
Chatterjee, T. K., Idelman, G., Blanco, V., Blomkalns, A. L., Piegore, M., Weintraub, D. S., Kumar, S., Rajsheker, S., Manka, D. R., Rudich, S. M., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.262964 · Cited by 151
Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase
Moreno-Yruela, C., Galleano, I., Madsen, A. S., & Olsen, C. A. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2018.04.007 · Cited by 149
Denis, G. V., McComb, M. E., Faller, D. V., Sinha, A., Romesser, P. B., & Costello, C. E. (2006) · Journal of Proteome Research · doi:10.1021/pr050430u · Cited by 144
Rachid, T. L., Penna‐de‐Carvalho, A., Bringhenti, I., Águila, M. B., Mandarim‐de‐Lacerda, C. A., & Souza‐Mello, V. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.12.027 · Cited by 143
Champigny, O., Ricquier, D., Blondel, O., Mayers, R. M., BRISCOE, M. G., & Holloway, B. R. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.23.10774 · Cited by 137
Wang, L., Teng, R., Di, L., Rogers, H. M., Wu, H., Kopp, J. B., & Noguchi, C. T. (2013) · Diabetes · doi:10.2337/db13-0518 · Cited by 124
Challenges in β 3 -adrenoceptor agonist drug development
Arch, J. R. S. (2011) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018811398517 · Cited by 121
Villicev, C. M., Freitas, F. R. S., Aoki, M. S., Taffarel, C., Scanlan, T. S., Moriscot, A. S., Ribeiro, M. O., Bianco, A. C., & Gouveia, C. H. A. (2007) · Journal of Endocrinology · doi:10.1677/joe.1.07066 · Cited by 120
Lin, J. Z., Martagón, A. J., Cimini, S. L., Gonzalez, D. D., Tinkey, D. W., Biter, A. B., Baxter, J. D., Webb, P., Gustafsson, J.-Α., Hartig, S. M., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.022 · Cited by 120
Li, F., Wu, R., Cui, X., Zha, L., Yu, L., Shi, H., & Xue, B. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.677930 · Cited by 119
Chatterjee, T. K., Basford, J. E., Knoll, E., Tong, W. S., Blanco, V., Blomkalns, A. L., Rudich, S. M., Lentsch, A. B., Hui, D. Y., & Weintraub, N. L. (2013) · Diabetes · doi:10.2337/db13-1148 · Cited by 107
Acute effect of L‐796568, a novel β3‐adrenergic receptor agonist, on energy expenditure in obese men
van Baak, M. A., Hul, G. B. J., Toubro, S., Astrup, A., Gottesdiener, K. M., DeSmet, M., & Saris, W. H. M. (2002) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2002.122527 · Cited by 103
Wang, H., Zhang, Y., Yehuda‐Shnaidman, E., Medvedev, A. V., Kumar, N., Daniel, K. W., Robidoux, J., Czech, M., Mangelsdorf, D. J., & Collins, S. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01479-07 · Cited by 101
Weiner, J., Kranz, M., Klöting, N., Kunath, A., Steinhoff, K. G., Rijntjes, E., Köhrle, J., Zeisig, V., Hankir, M. K., Gebhardt, C., et al. (2016) · Scientific Reports · doi:10.1038/srep38124 · Cited by 98
Histone/protein deacetylase 11 targeting promotes Foxp3+ Treg function
Huang, J., Wang, L., Dahiya, S., Beier, U. H., Han, R., Samanta, A., Bergman, J., Sotomayor, E. M., Seto, E., Kozikowski, A. P., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-09211-3 · Cited by 96
HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning
Ferrari, A., Longo, R., Fiorino, E., Silva, R., Mitro, N., Cermenati, G., Gilardi, F., Desvergne, B., Andolfo, A., Magagnotti, C., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00182-7 · Cited by 89
Crowe, B. L., Larue, R. C., Yuan, C., Hess, S., Kvaratskhelia, M., & Foster, M. P. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516813113 · Cited by 83
Structural Mechanism of Transcriptional Regulator NSD3 Recognition by the ET Domain of BRD4
Zhang, Q., Zeng, L., Shen, C., Ju, Y., Konuma, T., Zhao, C., Vakoc, C. R., & Zhou, M. (2016) · Structure · doi:10.1016/j.str.2016.04.019 · Cited by 78
Chatterjee, T. K., Basford, J. E., Yiew, K. H., Stepp, D. W., Hui, D. Y., & Weintraub, N. L. (2014) · Adipocyte · doi:10.4161/adip.28814 · Cited by 39
Tamucci, K. A., Namwanje, M., Fan, L., & Qiang, L. (2017) · Protein & Cell · doi:10.1007/s13238-017-0434-2 · Cited by 39
Investigating the effects of Orexin-A on thermogenesis in human deep neck brown adipose tissue
Pino, M. F., Divoux, A., Simmonds, A. V., Smith, S. R., & Sparks, L. M. (2017) · International Journal of Obesity · doi:10.1038/ijo.2017.155 · Cited by 26
Caregiving for Older Adults with Obesity in the United States
Ankuda, C. K., Harris, J. A., Ornstein, K. A., Levine, D. A., Langa, K. M., & Kelley, A. S. (2017) · Journal of the American Geriatrics Society · doi:10.1111/jgs.14918 · Cited by 7
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Metadata
- Authors
- 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., Pino, M. F., Sparks, L. M., Smith, S. R., Scherer, P. E., Collins, S., Seto, E., & McKinsey, T. A.
- Affiliations
- University of Colorado Anschutz (US)
- George Washington University (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Translational Research Institute for Metabolism and Diabetes (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- McKinsey, Timothy A.
- ORCID
- Venue
- JCI Insight
- Published
- 2018-08-09
- Volume
- 3
- Issue
- 15
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC6129125
- OpenAlex
- W2794856460
- Cited by
- 110
- References
- 64
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 13 · 2023: 13 · 2022: 12 · 2021: 16 · 2020: 16 · 2019: 9 · 2018: 1
- FWCI
- 7.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL116848,HL127240, AG043822), T32HL007822, F32HL126354).)
- American Heart Association (16SFRN31400013, 16POST30960017)
- Canadian Institutes of Health Research (FRN-216927)
- xxx (xxx)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- HDAC11, BRD2, brown adipose tissue, thermogenesis, beta-adrenergic signaling, obesity, insulin sensitivity, hepatic steatosis, energy homeostasis, epigenetic regulation, diabetes mellitus
- MeSH terms
- Bromodomain Containing Proteins, Adult, Aged, Aged, 80 and over, Animals, Adipose Tissue, Brown, Disease Models, Animal, Energy Metabolism, Fatty Liver, Female, Gene Expression Regulation, Histone Deacetylases, Humans, Insulin Resistance, Male, Middle Aged, Obesity, Transcription Factors, Mice, Knockout, Thermogenesis, Epigenesis, Genetic, Mice, Adipose Tissue, White, Diet, High-Fat
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