The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
Human brown adipose tissue is phenocopied by classical brown adipose tissue in physiologically humanized mice
Abstract
Human and rodent brown adipose tissues (BAT) appear morphologically and molecularly different. Here we compare human BAT with both classical brown and brite/beige adipose tissues of 'physiologically humanized' mice: middle-aged mice living under conditions approaching human thermal and nutritional conditions, that is, prolonged exposure to thermoneutral temperature (approximately 30 °C) and to an energy-rich (high-fat, high-sugar) diet. We find that the morphological, cellular and molecular characteristics (both marker and adipose-selective gene expression) of classical brown fat, but not of brite/beige fat, of these physiologically humanized mice are notably similar to human BAT. We also demonstrate, both in silico and experimentally, that in physiologically humanized mice only classical BAT possesses a high thermogenic potential. These observations suggest that classical rodent BAT is the tissue of choice for translational studies aimed at recruiting human BAT to counteract the development of obesity and its comorbidities.
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“On the other hand, recent work suggest that BAT of “humanized” mice is notably similar to human BAT (de Jong et al., 2019).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as de Jong et al., 2019
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Items 101–143 of 143
Wayland, J. L., Doll, J., Lawson, M. J., Stankiewicz, T. E., Oates, J. R., Sawada, K., Damen, M. S. M. A., Alarcon, P. C., Haslam, D. B., Trout, A. T., et al. (2023) · Nutrients · doi:10.3390/nu15234958 · Cited by 2
“Notably, TN housing increases adipocyte size in murine inguinal white adipose tissue (iWAT) [68] and causes mouse brown adipose tissue (BAT) to closely resemble human BAT [69].”
BackgroundHeimann, A. S., Singh, P., Ferro, E. S., Greenway, F. L., & Krongrad, A. (2025) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.70056 · Cited by 4
“White adipose tissue browning induces fat loss and remodelling through an increased activation of UCP1 gene expression [22, 47], which could be one of the possible Pep19 mechanisms of action in humans, as previously shown to occur in cellular and animal models [17, 22].”
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“One of the main strategies proposed to counteract obesity is an increase in energy expenditure through the activation of non-shivering thermogenesis (de Jong et al., 2019; Jagtap & Paul, 2023; Ruiz et al., 2018).”
Insulin Resistance and Cardiometabolic Syndrome
Kim, J. (2021) · CardioMetabolic Syndrome Journal · doi:10.51789/cmsj.2021.1.e9 · Cited by 3
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“56 Reduced number of unilocular and increased number of multilocular and paucilocular adipocytes in fasted animals reported in this study could be interpreted as a morphological sign of lipolysis.”
BackgroundHuo, M., Ye, J., Zhang, Y., Wang, M., Zhang, J., Feng, S., Cai, H., Zhong, B., & Dong, Z. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e27314 · Cited by 1
Li, L., & Feldman, B. J. (2025) · Stem Cell Reports · doi:10.1016/j.stemcr.2025.102509 · Cited by 1
Brown Adipose Tissue Thermogenesis
Blondin, D. P. (2026) · Physiology · doi:10.1152/physiol.00002.2026 · Cited by 1
Decoding Adipose Tissue Phenotypic Switching: From Mechanisms to Computational Drug Discovery
Ye, Y., Yin, R., Sun, J., Dai, Y., Zhao, D., & Zou, X. (2026) · Current Obesity Reports · doi:10.1007/s13679-026-00701-y · Cited by 1
“However, recent research demonstrates that the classical interscapular BAT in middle-aged mice closely models the key features of human supraclavicular BAT, supporting its translational relevance [28, 29].”
Metabolic inflammation, obesity, and cancer
Alzaïd, F., Blériot, C., Anagnostopoulos, G., Chakarov, S., Venteclef, N., & Ginhoux, F. (2026) · Immunity · doi:10.1016/j.immuni.2026.07.020 · Cited by 1
Wolfrum, C., & Challa, T. D. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.101897 · Cited by 1
“This approach is supported by data from De Jong et al., 2019 [10], who demonstrated that classical brown adipose tissue (BAT) in humanized middle-aged mice under thermoneutral conditions closely resembles human BAT, suggesting that our model is highly relevant for translating fi ndings to human…”
Yonemoto, E., Ihara, R., Tanaka, E., & Mitani, T. (2024) · Bioscience Biotechnology and Biochemistry · doi:10.1093/bbb/zbae105 · Cited by 1
Ahluwalia, R., Luijten, I. H. N., Filho, C. P. B. S., Braz, G. R. F., Petrovič, N., Shabalina, I. G., Cannon, B., & Nedergaard, J. (2025) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00038.2025 · Cited by 1
Giroud, M., Kotschi, S., Kwon, Y., Thuc, O. L., Hoffmann, A., Gil‐Lozano, M., Karbiener, M., Higareda‐Almaraz, J. C., Khani, S., Tews, D., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.09.455681 · Cited by 1
“30 °C [13], but humans are thermoneutral at much lower temperatures and, therefore, humans only display limited thermogenic activity [14], as their warm environment makes NST obsolete.”
BackgroundSupraclavicular brown adipocytes originate from Tbx1 + myoprogenitorsPreprint
Huang, Z., Gu, C., Zhang, Z., Arianti, R., Swaminathan, A., Tran, K., Battist, A., Kristóf, E., & Ruan, H. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.16.545229 · Cited by 1
The paper that found a third form of fat cell
Oldach, L. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100817
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Lynch, L. (2021) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.738227474.793583818
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“Thermoneutral BAT is closer to human BAT and could be used in future experiments – particularly those relating to biological sex differences 79,80 .”
BackgroundBerthelsen, L. O., Skydsgaard, M., & Nedergaard, J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-12-821046-8.00004-9
Liu, X., Tang, J., Zhang, R., Zhan, S., Zhong, T., Guo, J., Wang, Y., Cao, J., Li, L., Zhang, H., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20353537
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Liu, X., Tang, J., Zhang, R., Zhan, S., Zhong, T., Guo, J., Wang, Y., Cao, J., Li, L., Zhang, H., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20353531
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Liu, X., Tang, J., Zhang, R., Zhan, S., Zhong, T., Guo, J., Wang, Y., Cao, J., Li, L., Zhang, H., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20353534
Bast‐Habersbrunner, A., & Klingenspor, M. (2024) · Springer eBooks · doi:10.1007/978-3-662-58895-6_16
Effects of therapeutic factors on brown adipose tissue in order to correct obesity
Kurmaev, D. P., Bulgakova, S. V., Treneva, E. V., & Merzlova, P. Y. (2025) · Экспериментальная и клиническая гастроэнтерология · doi:10.31146/1682-8658-ecg-228-8-7-27
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Sympathetic signaling directs macrophage efferocytosis in thermogenic adipose tissuePreprint
Meyer, S., Witt, J., Liebold, I., López-López, T., Ehlen, L., Leyk, S., Hiefner, J., Haas, D. T., Schlein, C., Sáez, P. J., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.28.685032
“Applying these “physiologically humanized” conditions, result in the presence of enlarged unilocular adipocytes and moderate immune cell infiltration, including macrophages, into BAT ( 58 , 59 ).”
Tóth, B. B., Barta, Z., Barta, Á. B., & Fésüs, L. (2021) · Figshare · doi:10.6084/m9.figshare.17163062
Liu, X., Tang, J., Zhang, R., Zhan, S., Zhong, T., Guo, J., Wang, Y., Cao, J., Li, L., Zhang, H., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20353546
Tóth, B. B., Barta, Z., Barta, Á. B., & Fésüs, L. (2021) · Figshare · doi:10.6084/m9.figshare.17163056
Tóth, B. B., Barta, Z., Barta, Á. B., & Fésüs, L. (2021) · Figshare · doi:10.6084/m9.figshare.17163065
Tóth, B. B., Barta, Z., Barta, Á. B., & Fésüs, L. (2021) · Figshare · doi:10.6084/m9.figshare.17163032
Tóth, B. B., Barta, Z., Barta, Á. B., & Fésüs, L. (2021) · Figshare · doi:10.6084/m9.figshare.17163059
Cold exposure and metabolic health: Therapeutic potential for obesity, diabetes, and beyond
Li, X., Dang, J., Guo, R., Griffiths, H. R., Lu, S., & Gao, D. (2026) · Physiological Reports · doi:10.14814/phy2.70838
“In contrast, adult human BAT contains discrete islands of multilocular adipocytes surrounded by unilocular adipocytes, a feature similar to that of murine beige adipose tissue under mild cold conditions (21°C) (Cannon et al., 2020; de Jong et al., 2019).”
Humanes braunes Fett – Viel Evidenz und ein wenig Utopie
Jung, A. S., & Bartelt, A. (2026) · Adipositas - Ursachen Folgeerkrankungen Therapie · doi:10.1055/a-2776-4782
“…tion bei Menschen primär durch Muskelzittern und eine gesteigerte myokardiale Thermogenese getragen wird, während die oxidative Aktivität von BAT ein „Alles-oder-Nichts“-Verhal-braun Faktoren wie Umgebungstemperatur und Ernährung für BAT-Aktivi-tät sind, zeigte eine Mausstudie von Jong et al [30].”
Only a fraction of UCP1 is required to sustain adaptive nonshivering thermogenesis in the coldPreprint
Qimuge, N., Filho, C. P. B. S., 庞卫军, & Petrovič, N. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.06.743367
“3-8 ) has led to the widespread assumption that these adipocytes are major contributors to adaptive nonshivering thermogenesis.”
Metadata
- Authors
- de Jong, J. M. A., Sun, W., Pires, N. D., Frontini, A., Balaz, M., Jespersen, N. Z., Feizi, A., Petrovic, K., Fischer, A. W., Bokhari, M. H., Niemi, T., Nuutila, P., Cinti, S., Nielsen, S., Scheele, C., Virtanen, K., Cannon, B., Nedergaard, J., Wolfrum, C., & Petrovic, N.
- Affiliations
- ETH Zurich (CH)
- University of Pavia (IT)
- University of Copenhagen (DK)
- Harvard University (US)
- Stockholm University (SE)
- Turku University Hospital (FI)
- University of Turku (FI)
- Copenhagen University Hospital (DK)
- ORCID
- Venue
- Nature Metabolism
- Published
- 2019-08-19
- Volume
- 1
- Issue
- 8
- Pages
- 830-843
- ISSN
- 2522-5812 (ISSN-L)
- OpenAlex
- W2969227545
- Cited by
- 137
- References
- 74
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 18 · 2023: 18 · 2022: 23 · 2021: 27 · 2020: 25 · 2019: 3
- FWCI
- 14.41
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-09-10)
- Open access
- closed
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Vetenskapsrådet
- 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
- brown adipose tissue, thermoneutrality, high-fat high-sugar diet, thermogenesis, obesity, translational model, adipose tissue gene expression, adipose tissue morphology
- MeSH terms
- Animals, Adipose Tissue, Brown, Humans, Thermogenesis, Mice
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