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Adaptive thermogenesis in adipocytes: Is beige the new brown?
Open accessAbstract
One of the most promising areas in the therapeutics for metabolic diseases centers around activation of the pathways of energy expenditure. Brown adipose tissue is a particularly appealing target for increasing energy expenditure, given its amazing capacity to transform chemical energy into heat. In addition to classical brown adipose tissue, the last few years have seen great advances in our understanding of inducible thermogenic adipose tissue, also referred to as beige fat. A deeper understanding of the molecular processes involved in the development and function of these cell types may lead to new therapeutics for obesity, diabetes, and other metabolic diseases.
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“Brite adipocytes can express UCP1 and, as such, can participate in the maintenance of body temperature 90.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [90]
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“This process is characterized by the appearance of brite (from brown‐in‐white) adipocytes, also called beige adipocytes, mainly in subcutaneous WAT.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [90]
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“The determination, differentiation, and metabolic functions of thermogenic adipocytes are under the control of a growing list of extracellular signaling cues, transcription factors and cofactors, and microRNAs [58-61].”
BackgroundHealth benefits of fucoxanthin in the prevention of chronic diseases
Bae, M., Kim, M., Park, Y., & Lee, J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2020.158618 · Cited by 198
Burn Induces Browning of the Subcutaneous White Adipose Tissue in Mice and Humans
Patsouris, D., Qi, P., Abdullahi, A., Stanojcic, M., Chen, P., Parousis, A., Amini‐Nik, S., & Jeschke, M. G. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.028 · Cited by 186
“UCP1 is the only exclusively expressed in adipose-specific depots, in particular, the brown adipose tissue (Wu et al., 2013).”
Wu, M. V., Bikopoulos, G. J., Hung, S., & Ceddia, R. B. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.591008 · Cited by 187
Adipose Tissue Fibrosis in Obesity: Etiology and Challenges
Marcelin, G., Gautier, E. L., & Clément, K. (2021) · Annual Review of Physiology · doi:10.1146/annurev-physiol-060721-092930 · Cited by 201
Fu, T., Seok, S., Choi, S., Huang, Z., Suino-Powell, K. M., Xu, H. E., KEMPER, B. W., & Kemper, J. K. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00596-14 · Cited by 190
Inter‐organ communication: a gatekeeper for metabolic health
Castillo‐Armengol, J., Fajas, L., & Lopez‐Mejia, I. C. (2019) · The EMBO Reports · doi:10.15252/embr.201947903 · Cited by 178
“Brite adipocytes can express UCP1 and, as such, can participate in the maintenance of body temperature [90].”
Lee, M.-W., Lee, M., & Oh, K. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8060854 · Cited by 192
“However, it has recently been reported that AT also functions as an energy-consuming organ that participates in the regulation of thermogenesis, the process that dissipates energy in the form of heat [16,17].”
BackgroundArble, D. M., Bass, J., Behn, C. D., Butler, M. P., Challet, E., Czeisler, C., Depner, C. M., Elmquist, J., Franken, P., Grandner, M. A., et al. (2015) · Sleep · doi:10.5665/sleep.5226 · Cited by 173
MicroRNA-26 Family Is Required for Human Adipogenesis and Drives Characteristics of Brown Adipocytes
Karbiener, M., Pisani, D. F., Frontini, A., Oberreiter, L. M., Lang, E., Vegiopoulos, A., Mössenböck, K., Bernhardt, G. A., Mayr, T., Hildner, F., et al. (2013) · Stem Cells · doi:10.1002/stem.1603 · Cited by 176
Brain regulation of energy balance and body weight
Rui, L. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9261-9 · Cited by 168
“Beige adipocytes have many brown adipocyte characteristics, including high levels of mitochondria, UCP1 expression, and energy dissipation as heat, and beige cell differentiation and activity are highly inducible [199].”
BackgroundWnt/β-Catenin Signaling and Obesity
Chen, N., & Wang, J. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00792 · Cited by 173
Myocardin-Related Transcription Factor A Regulates Conversion of Progenitors to Beige Adipocytes
McDonald, M. E., Li, C., Bian, H.-J., Smith, B. D., Layne, M. D., & Farmer, S. R. (2015) · Cell · doi:10.1016/j.cell.2014.12.005 · Cited by 167
“The MRTFA-associated browning of iWAT likely arises through recruitment of beige progenitors, as opposed to transdifferentiation of mature white adipocytes (Barbatelli et al., 2010; Wu et al., 2012, 2013).”
Fried, S. K., Lee, M., & Karastergiou, K. (2015) · Obesity · doi:10.1002/oby.21133 · Cited by 167
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
Contreras, C., González, F., Fernø, J., Diéguez, C., Rahmouni, K., Nogueiras, R., & López, M. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.919727 · Cited by 167
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 166
Brown and Beige Adipose Tissues in Health and Disease
Rui, L. (2017) · Comprehensive physiology · doi:10.1002/cphy.c170001 · Cited by 186
“levels by a homeostatic mechanism in adulthood; in contrast, beige fat is barely detectable at thermoneutrality and highly induced by cold exposure (18, 103, 338, 339).”
Proinflammatory Phenotype of Perivascular Adipocytes
Omar, A., Chatterjee, T. K., Tang, Y., Hui, D. Y., & Weintraub, N. L. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303030 · Cited by 159
GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1
Xu, F., Lin, B., Zheng, X., Chen, Z., Cao, H., Xu, H., Liang, H., & Weng, J. (2016) · Diabetologia · doi:10.1007/s00125-016-3896-5 · Cited by 157
A comparative perspective on lipid storage in animals
Birsoy, K., Festuccia, W. T., & Laplante, M. (2013) · Journal of Cell Science · doi:10.1242/jcs.104992 · Cited by 163
Turn up the power - pharmacological activation of mitochondrial biogenesis in mouse models
Komen, J. C., & Thorburn, D. R. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12413 · Cited by 149
“Whole-body energy balance is a key concept in these disorders, with a long-standing interest in the role of brown fat, which is rich in mitochondria and can dissipate energy efficiently through non-shivering thermogenesis due to high levels of the uncoupling protein 1 (Wu et al., 2013).”
BackgroundHuman and Mouse Brown Adipose Tissue Mitochondria Have Comparable UCP1 Function
Porter, C., Herndon, D. N., Chondronikola, M., Chao, T., Annamalai, P., Bhattarai, N., Saraf, M. K., Capek, K. D., Reidy, P. T., Daquinag, A. C., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.004 · Cited by 148
“…BAT to alter energy balance in humans, significant efforts have been made to understand the lineage (Jespersen et al., 2013; Shinoda et al., 2015; Wu et al., 2012, 2013), genetic signature (Cypess et al., 2013; Shinoda et al., 2015; Wu et al., 2012, 2013; Xue et al., 2015), and thermogenic…”
Flachs, P., Rossmeisl, M., Kuda, O., & Kopecký, J. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.02.003 · Cited by 154
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
Li, G., Xie, C., Lu, S., Nichols, R. G., Tian, Y., Li, L., Patel, D., Ma, Y., Brocker, C. N., Yan, T., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.007 · Cited by 144
Vitamin D and energy homeostasis—of mice and men
Bouillon, R., Carmeliet, G., Lieben, L., 渡辺, 光., Perino, A., Auwerx, J. H., Schoonjans, K., & Verstuyf, A. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.226 · Cited by 149
Mechanisms Linking Excess Adiposity and Carcinogenesis Promotion
Pérez-Hernández, A. I., Catalán, V., Gómez‐Ambrosi, J., RodrÃguez, A., & Frühbeck, G. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00065 · Cited by 148
“Recently, the existence of a third kind of adipose tissue has been proposed, the “beige” or “brite” (brown-like adipocytes) adipose tissue (97).”
BackgroundThermogenic adipocytes promote HDL turnover and reverse cholesterol transport
Bartelt, A., John, C., Schaltenberg, N., Berbée, J. F. P., Worthmann, A., Cherradi, M. L., Schlein, C., Piepenburg, J., Boon, M. R., Rinninger, F., et al. (2017) · Nature Communications · doi:10.1038/ncomms15010 · Cited by 138
Role of adipose specific lipid droplet proteins in maintaining whole body energy homeostasis
Konige, M., Wang, H., & Sztalryd, C. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.05.007 · Cited by 150
“The current thinking is that beige cells and brown fat cells come from separate cell lineages [30].”
BackgroundGhesmati, Z., Rashid, M., Fayezi, S., Gieseler, F., Alizadeh, E., & Darabi, M. (2024) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09850-0 · Cited by 139
“The expression of important transcription factors such as PRDM16 , PPARA , and UCP1 (as a hallmark of thermogenesis) has been observed in WAT [240].”
BackgroundWanders, D., Stone, K. P., Forney, L. A., Cortez, C. C., Dille, K. N., Simon, J., Xu, M., Hotard, E. C., Nikonorova, I. A., Pettit, A. P., et al. (2016) · Diabetes · doi:10.2337/db15-1324 · Cited by 138
“Experiments 1 and 2 Browning of WAT contributes to increased EE in rodents (31), and chronic MR (11 weeks) induces significant browning of WAT in mice (32).”
Backgroundde 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
The Whitening of Brown Fat and Its Implications for Weight Management in Obesity
Shimizu, I., & Walsh, K. X. (2015) · Current Obesity Reports · doi:10.1007/s13679-015-0157-8 · Cited by 141
Xu, L., & Ota, T. (2017) · Adipocyte · doi:10.1080/21623945.2017.1413516 · Cited by 134
“Indeed, brown-like adipocytes have anti-obesity and antidiabetic effects in rodent models [51].”
Background
Metadata
- Authors
- Wu, J., Cohen, P., & Spiegelman, B. M.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-02-01
- Volume
- 27
- Issue
- 3
- Pages
- 234-250
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3576510
- OpenAlex
- W2170874580
- Cited by
- 828
- References
- 204
- Citations by year
- 2026: 22 · 2025: 29 · 2024: 34 · 2023: 37 · 2022: 46 · 2021: 64 · 2020: 64 · 2019: 72 · 2018: 56 · 2017: 91 · 2016: 73 · 2015: 98 · 2014: 91 · 2013: 46
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Foundation for the National Institutes of Health
- American Heart Association
- JPB Foundation
- National Institutes of Health (DK31405)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK031405, DK-31405, K01DK094824, RC4DK090861, DK90861, R37DK031405)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- beige adipocytes, brown adipose tissue, thermogenesis, energy expenditure, adaptive thermogenesis, obesity, diabetes mellitus, metabolic disorders, adipogenesis
- MeSH terms
- Uncoupling Protein 1, Adaptation, Physiological, Animals, Adipose Tissue, Brown, Humans, Ion Channels, Obesity, Adipocytes, Gene Expression Regulation, Developmental, Thermogenesis, Mitochondrial Proteins
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