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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Recent work suggests that BAT of humanized mice is notably similar to human BAT.
“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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BackgroundAn update on brown adipose tissue biology: a discussion of recent findings
Gaspar, R. C., Pauli, J. R., Shulman, G. I., & Muñoz, V. R. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00310.2020 · Cited by 91 · see citing works
Emerging debates and resolutions in brown adipose tissue research
Cypess, A. M., Cannon, B., Nedergaard, J., Kazak, L., Chang, D. C., Krakoff, J. A., Tseng, Y., Scheele, C. C., Boucher, J., Petrovič, N., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.11.002 · Cited by 84 · see citing works
Brown Adipose Tissue Heterogeneity, Energy Metabolism, and Beyond
Shinde, A. B., Song, A., & Wang, Q. A. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.651763 · Cited by 80 · see citing works
“They also found that the BAT of these mice closely resembles that of adult humans both morphologically as well as transcriptionally (60).”
BackgroundMartínez‐Téllez, B., Sánchez‐Delgado, G., Acosta, F. M., Alcántara, J. M. A., Amaro‐Gahete, F. J., Martinez-Avila, W. D., Merchán-Ramírez, E., Muñoz-Hernández, V., Osuna‐Prieto, F. J., Jurado‐Fasoli, L., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32502-x · Cited by 73 · see citing works
Magnetic Resonance Imaging Techniques for Brown Adipose Tissue Detection
Wu, M., Junker, D., Branca, R. T., & Karampinos, D. C. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00421 · Cited by 63 · see citing works
“Histological analysis of human supraclavicular fat has shown that the area contains only small clusters of multilocular brown adipocytes, mixed with WAT (1, 4, 75).”
BackgroundInfluentialHuman brown adipose tissue: Classical brown rather than brite/beige?
Cannon, B., de Jong, J. M. A., Fischer, A. W., Nedergaard, J., & Petrovič, N. (2020) · Experimental Physiology · doi:10.1113/ep087875 · Cited by 62 · see citing works
“However, the brite/beige adipocytes isolated from older mice had completely lost this ability (whichwaspresent in brite/beige adipocytes isolated fromyoungmice; de Jong et al., 2019).”
BackgroundMethodInfluentialMaurer, S., Harms, M., & Boucher, J. (2020) · FEBS Journal · doi:10.1111/febs.15470 · Cited by 61 · see citing works
Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution
Schlein, C., Fischer, A. W., Sass, F., Worthmann, A., Tödter, K., Jaeckstein, M. Y., Behrens, J. R., Lynes, M. D., Kiebish, M. A., Narain, N. R., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108624 · Cited by 57 · see citing works
Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes.
Wang, T., Sharma, A., Wu, C., Maushart, C., Ghosh, A., Yang, W., Stefanicka, P., Kovaničová, Z., Ukropec, J., Zhang, J., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.07.005 · Cited by 67 · see citing works
CLSTN3β enforces adipocyte multilocularity to facilitate lipid utilization
Qian, K., Tol, M. J. P. M., Wu, J., Uchiyama, L. F., Xu, X., Cui, L., Bedard, A. H., Weston, T. A., Rajendran, P. S., Vergnes, L., et al. (2022) · Nature · doi:10.1038/s41586-022-05507-1 · Cited by 56 · see citing works
Brown adipose tissue involution associated with progressive restriction in progenitor competence
Huang, Z., Zhang, Z.-D., Moazzami, Z., Heck, R., Hu, P., Nanda, H. A., Ren, K., Sun, Z., Bartolomucci, A., Gao, Y., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110575 · Cited by 44 · see citing works
Impact of Adaptive Thermogenesis in Mice on the Treatment of Obesity
Bastías-Pérez, M., Zagmutt, S., Soler‐Vázquez, M. C., Serra, D., Mera, P., & Herrero, L. (2020) · Cells · doi:10.3390/cells9020316 · Cited by 53 · see citing works
“Under this situation, cold-induced thermogenesis would be minimal and will not influence total energy expenditure [97].”
BackgroundBartke, A., Brannan, S., Hascup, E. R., Hascup, K. N., & Darcy, J. (2020) · The World Journal of Men s Health · doi:10.5534/wjmh.200112 · Cited by 48 · see citing works
“There is increasing evidence that studying mice living at temperatures corresponding to their thermoneutral zone is important for obtaining data that can be “translatable” to humans [35-37].”
BackgroundEffects of Caffeine on Brown Adipose Tissue Thermogenesis and Metabolic Homeostasis: A Review
Schaik, L. V., Kettle, C., Green, R., Irving, H. R., & Rathner, J. A. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.621356 · Cited by 48 · see citing works
Huo, C., Song, Z., Yin, J., Zhu, Y., Miao, X., Qian, H., Wang, J., Ye, L., & Zhou, L. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.917084 · Cited by 45 · see citing works
Aldiss, P., Lewis, J. E., Lupini, I., Bloor, I. D., Chavoshinejad, R., Boocock, D. J., Miles, A. K., Ebling, F. J. P., Budge, H., & Symonds, M. E. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00097 · Cited by 41 · see citing works
“Importantly, BAT from obese mice housed chronically at thermoneutrality, closer resembles human BAT and this model of “physiologically humanized BAT” represents the best choice for modeling BAT physiology (22).”
BackgroundArchitecture of the outbred brown fat proteome defines regulators of metabolic physiology
Xiao, H., Bozi, L. H. M., Sun, Y., Riley, C. L., Philip, V. M., Chen, M., Li, J., Zhang, T., Mills, E. L., Emont, M. P., et al. (2022) · Cell · doi:10.1016/j.cell.2022.10.003 · Cited by 41 · see citing works
Two-stage evolution of mammalian adipose tissue thermogenesis
Keipert, S., Gaudry, M. J., Kutschke, M., Keuper, M., Rosa, M. A. S. D., Cheng, Y., Kuhn, J. M. M., Laterveer, R., Cotrim, C. A., Giere, P., et al. (2024) · Science · doi:10.1126/science.adg1947 · Cited by 39 · see citing works
Studying Brown Adipose Tissue in a Human in vitro Context
Samuelson, I., & Vidal‐Puig, A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00629 · Cited by 37 · see citing works
“In contrast, a recent study suggests that when mice are physiologically humanized, meaning housed at thermoneutrality, fed a “Western diet,” and examined at 9– 11 months old, their BAT becomes comparable with human supraclavicular BAT (23), although this conclusion has raised some discussion (24).”
BackgroundGong, D., Lei, J., He, X., Hao, J., Zhang, F., Huang, X., Gu, W., Yang, X., & Yu, J. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02300-z · Cited by 36 · see citing works
“Additionally, the summarization of factors that stimulate UCP1 activation is limited, and not all factors are fully understood.”
Sass, F., Schlein, C., Jaeckstein, M. Y., Pertzborn, P., Schweizer, M., Schinke, T., Ballabio, A., Scheja, L., Heeren, J., & Fischer, A. W. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101173 · Cited by 35 · see citing works
Cold exposure induces lipid dynamics and thermogenesis in brown adipose tissue of goats
Liu, X., Tang, J., Zhang, R., Zhan, S., Zhong, T., Guo, J., Wang, Y., Cao, J., Li, L., Zhang, H., et al. (2022) · BMC Genomics · doi:10.1186/s12864-022-08765-5 · Cited by 35 · see citing works
Korobkina, E. D., Calejman, C. M., Haley, J. D., Kelly, M. E., Li, H., Gaughan, M., Chen, Q., Pepper, H. L., Ahmad, H., Boucher, A., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01143-3 · Cited by 34 · see citing works
“At the standard vivarium temperature of 22 °C, mice have highly thermogenic BAT because they are below their thermoneutral zone 22 .”
Septal LYVE1 + macrophages control adipocyte stem cell adipogenic potential
Yu, X., Hu, Y., Lim, H. Y., Li, Z., Jaitin, D. A., Yang, K. L., Kong, W. T., Xu, J., Bejarano, D. A., Bied, M., et al. (2025) · Science · doi:10.1126/science.adg1128 · Cited by 35 · see citing works
De Novo Lipogenesis as a Source of Second Messengers in Adipocytes
Hsiao, W., & Guertin, D. A. (2019) · Current Diabetes Reports · doi:10.1007/s11892-019-1264-9 · Cited by 34 · see citing works
Resistance exercise training induces subcutaneous and visceral adipose tissue browning in Swiss mice
Picoli, C. C., Gilio, G. R., Henriques, F. D. S., Leal, L. G., Besson, J. C. F., Lopes, M. A., de Moraes, S. M. F., Hernandes, L., Júnior, M. L. B., & Peres, S. B. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00742.2019 · Cited by 33 · see citing works
Thermogenic adipose tissue in energy regulation and metabolic health
Xue, S., Lee, D. P. H., & Berry, D. C. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1150059 · Cited by 30 · see citing works
McKie, G. L., Medak, K. D., Shamshoum, H., & Wright, D. C. (2022) · The FASEB Journal · doi:10.1096/fj.202101905rr · Cited by 30 · see citing works
Magnetic resonance imaging of obesity and metabolic disorders: Summary from the 2019 ISMRM Workshop
Hu, P., Branca, R. T., Hernando, D., Karampinos, D. C., Machann, J., McKenzie, C. A., Wu, H. H., Yokoo, T., & Velan, S. S. (2019) · Magnetic Resonance in Medicine · doi:10.1002/mrm.28103 · Cited by 29 · see citing works
Kukkonen, J. P., Jacobson, L. H., Hoyer, D., Rinne, M. K., & Borgland, S. L. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.123.000953 · Cited by 28 · see citing works
Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue
Dieckmann, S., Maurer, S., Fromme, T., Colson, C., Virtanen, K. A., Amri, E., & Klingenspor, M. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00073 · Cited by 26 · see citing works
“Although the presence of functional BAT has been confirmed in adult humans (4–6), humans mostly live under thermoneutral conditions (7).”
BackgroundInfluentialQuantification of adipocyte numbers following adipose tissue remodeling
Moser, C., Straub, L. G., Rachamin, Y., Dapito, D. H., Kulenkampff, E., Ding, L., Sun, W., Modica, S., Baláž, M., & Wolfrum, C. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109023 · Cited by 27 · see citing works
Therapeutic Perspectives of Thermogenic Adipocytes in Obesity and Related Complications
Wang, C., & Wei, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137177 · Cited by 25 · see citing works
Brown Adipose Tissue: A Metabolic Regulator in a Hypothalamic Cross Talk?
Henningsen, J. B., & Scheele, C. C. (2020) · Annual Review of Physiology · doi:10.1146/annurev-physiol-032420-042950 · Cited by 24 · see citing works
Zapata, J. L., Gallardo, A., Romero, C., Valenzuela, R., Garcia-Diaz, D., Duarte-Silva, L., Bustamante, A., Gasaly, N., Gotteland, M., & Echeverría, F. (2021) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2021.102388 · Cited by 24 · see citing works
Metabolomic Profiles of Mouse Tissues Reveal an Interplay between Aging and Energy Metabolism
Zhou, Q., Kerbl-Knapp, J., Zhang, F., Korbelius, M., Kuentzel, K. B., Vujić, N., Akhmetshina, A., Hörl, G., Paar, M., Steyrer, E., et al. (2021) · Metabolites · doi:10.3390/metabo12010017 · Cited by 25 · see citing works
“Adipose tissues of human and mice have various heterogeneities [68,69], here we aimed to decipher the possible common mechanisms of aging despite these diversities.”
Backgroundde Lange, P., Lombardi, A., Silvestri, E., Cioffi, F., Giacco, A., Iervolino, S., Petito, G., Senese, R., Lanni, A., & Moreno, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411676 · Cited by 26 · see citing works
Biagi, C., Cury, S., Alves, C. P., Rabhi, N., Silva, W. A., Farmer, S., Carvalho, R., & Batista, M. (2021) · bioRxiv · doi:10.3390/cells10113073 · Cited by 13 · see citing works
“However, the interest in their physiological function and therapeutic potential to combat obesity has only recently been revisited after discovering the thermogenic response of white adipocytes in adult humans [5,14].”
BackgroundStanić, S., Bardová, K., Janovská, P., Rossmeisl, M., Kopecký, J., & Zouhar, P. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116042 · Cited by 20 · see citing works
Fischer, A. W., Behrens, J. R., Sass, F., Schlein, C., Heine, M., Pertzborn, P., Scheja, L., & Heeren, J. (2020) · Journal of Lipid Research · doi:10.1194/jlr.ra119000455 · Cited by 21 · see citing works
Sánchez‐Delgado, G., Martínez‐Téllez, B., Acosta, F. M., Virtue, S., Vidal‐Puig, A., Gil, Á., Elvira, J. M. L., & Ruiz, J. R. (2021) · Diabetes · doi:10.2337/db21-0011 · Cited by 20 · see citing works
Dani, V., Yao, X., & Dani, C. (2021) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09632-6 · Cited by 19 · see citing works
Liao, F., Yao, C., Chen, S., Wu, T., & Lin, S. (2022) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.2c00628 · Cited by 19 · see citing works
Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue
Carobbio, S., Guénantin, A.-C., Bahri, M., Rodríguez‐Fdez, S., Honig, F., Kamzolas, I., Samuelson, I., Long, K. R., Awad, S., Lukovic, D., et al. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.01.013 · Cited by 19 · see citing works
“Despite the claim that human BAT resembles more murine beige cells than murine BAT (Sharp et al., 2012; Shinoda et al., 2015), recent data indicate that human BAT and murine BAT exhibit similar histology and transcriptional patterns when mice are at thermoneutrality (30 C) (de Jong et al., 2019).”
BackgroundConfounding issues in the ‘humanized’ BAT of mice
Kajimura, S., & Spiegelman, B. M. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0192-y · Cited by 19 · see citing works
Stojchevski, R., Chandrasekaran, P., Hadzi‐Petrushev, N., Mladenov, M. I., & Avtanski, D. B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147849 · Cited by 18 · see citing works
Cold Exposure Drives Weight Gain and Adiposity following Chronic Suppression of Brown Adipose Tissue
Aldiss, P., Lewis, J. E., Lupini, I., Bloor, I. D., Chavoshinejad, R., Boocock, D. J., Miles, A. K., Ebling, F. J. P., Budge, H., & Symonds, M. E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031869 · Cited by 18 · see citing works
“Importantly, it was recently demonstrated that BAT from obese mice, housed chronically at thermoneutrality closely resembles human BAT [4].”
BackgroundFang, Y., McFadden, S., Darcy, J., Hascup, E. R., Hascup, K. N., & Bartke, A. (2020) · Aging Cell · doi:10.1111/acel.13123 · Cited by 18 · see citing works
“Indeed, a recent study demonstrating that brown adipose tissue (BAT) from mice housed at thermoneutrality is more similar to that of humans, and therefore has more translatability, has gained considerable attention in the metabolism field (de Jong et al., 2019).”
BackgroundFischer, A. W., de Jong, J. M. A., Sass, F., Schlein, C., Heeren, J., & Petrovič, N. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.568682 · Cited by 18 · see citing works
“org 2 Physiologically Humanized Conditions The samples analyzed in this study were from the wild-type mice (C57BL/6) described and metabolically characterized in (7) and molecularly and morphologically analyzed in (2).”
BackgroundMethodInfluentialThermogenic genes are blunted whereas brown adipose tissue identity is preserved in human obesityPreprint
Jespersen, N. Z., Andersen, M. W., Hirschberg, V., Stærkær, T. W., Severinsen, M. C. K., Peijs, L., Soares, R., Forss, I., Andersen, E. S., Hahn, C. H., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.07.082057 · Cited by 18 · see citing works
Highly recruited brown adipose tissue does not in itself protect against obesity
von Essen, G., Lindsund, E., Maldonado, E. M., Zouhar, P., Cannon, B., & Nedergaard, J. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101782 · Cited by 17 · see citing works
“As we humans spend most of our time under thermoneutral conditions [59,60], any facultative diet-induced thermogenesis that exists should be manifest in humans.”
BackgroundAouichat, S., Raya, E., Molina‐Carballo, A., Muñoz‐Hoyos, A., Aloweidi, A. S., Elmahallawy, E. K., & Agil, A. (2022) · Antioxidants · doi:10.3390/antiox11091646 · Cited by 17 · see citing works
Pernes, G., Morgan, P. K., Huynh, K., Mellett, N. A., Meikle, P. J., Murphy, A. J., Henstridge, D. C., & Lancaster, G. I. (2020) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00112.2020 · Cited by 16 · see citing works
Mae, J., Nagaya, K., Okamatsu-Ogura, Y., Tsubota, A., Matsuoka, S., Nio-Kobayashi, J., & Kimura, K. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.698692 · Cited by 6 · see citing works
“Since human BAT is a mixture of classical brown and beige adipocytes (Wu et al., 2012; de Jong et al., 2019) and surrounded by white adipocytes in most cases (Saito et al., 2009; Zingaretti et al., 2009), the regulation of adipogenesis through cell–cell interaction may be important.”
BackgroundSkeletal muscle, not adipose tissue, mediates cold-induced metabolic benefits
Townsend, L. K., Wang, D., Wright, D. C., & Blondin, D. P. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00837-4 · Cited by 15 · see citing works
Involution of brown adipose tissue through a Syntaxin 4 dependent pyroptosis pathway
Yu, X., Benitez, G., Wei, P. T., Krylova, S. V., Song, Z., Liu, L. P., Zhang, M., Xiaoli, A. M., Wei, H., Chen, F., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46944-y · Cited by 15 · see citing works
“This degenerative process can also be mimicked by maintaining mice at ther-moneutrality (~28 – 30 °C) or by chronic high-fat diet feeding 21,25 .”
BackgroundThe obesity‐linked human lncRNA AATBC stimulates mitochondrial function in adipocytes
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. (2023) · EMBO Reports · doi:10.15252/embr.202357600 · Cited by 15 · see citing works
“In mice, thermoneu-trality is ca. 30 ° C (Cannon & Nedergaard, 2011), but humans are thermoneutral at much lower temperatures and, therefore, humans only display limited thermogenic activity (de Jong et al , 2019).”
BackgroundNguyen, V. T.-T., Vu, V. V., & Pham, P. V. (2023) · Adipocyte · doi:10.1080/21623945.2023.2237164 · Cited by 14 · see citing works
Pinto, Y. O., Festuccia, W. T., & Magdalon, J. (2022) · HORMONES · doi:10.1007/s42000-022-00361-2 · Cited by 12 · see citing works
Pani, S., Dey, S., Pati, B., Senapati, U., & Bal, N. (2022) · Journal of the Endocrine Society · doi:10.1210/jendso/bvac151 · Cited by 11 · see citing works
The Influence of Ambient Temperature on Adipose Tissue Homeostasis, Metabolic Diseases and Cancers
Ginting, R. P., Lee, J.-M., & Lee, M.-W. (2023) · Cells · doi:10.3390/cells12060881 · Cited by 11 · see citing works
Zhuang, Y., Zhang, X., Zhang, S., Sun, Y., Wang, H., Chen, Y., Zhang, H., Zou, P., Feng, Y., Lü, X., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59618-0 · Cited by 11 · see citing works
“Thermoneutral housing in combination with HFD can be used to thermally humanize mice 38 , and BAT from mice housed under such conditions remarkably resembles human BAT 3,38 .”
Du, K., Chen, G.-H., Bai, X., Chen, L., Hu, S., Li, Y., Wang, G., He, J.-W., & Lai, S. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.981661 · Cited by 10 · see citing works
Sympathetic innervation of the supraclavicular brown adipose tissue: A detailed anatomical study
Mori, S., Beyer, R. S., Bernardes‐Souza, B., Sorg, J. M., Hoover, D. B., Sacks, H. S., Fishbein, M. C., Chang, G., Peacock, W. J., John, M. A. S., et al. (2023) · PLoS ONE · doi:10.1371/journal.pone.0290455 · Cited by 10 · see citing works
“This is, in part, because BAT depots in humans are not identical to those in mice, in terms of distribution, molecular and anatomic morphology, and innervation [12].”
In-vivo detection of white adipose tissue browning: a multimodality imaging approach
Holmes, L. R., Garside, J. C., Frank, J., Livingston, E. W., Snyder, J., Khalaf, N., Yuan, H., & Branca, R. T. (2023) · Scientific Reports · doi:10.1038/s41598-023-42537-9 · Cited by 9 · see citing works
Przygodda, F., Lautherbach, N. E. S., Buzelle, S. L., Gonçalves, D. A. P., de Assis, A. P., Paula-Gomes, S., Garófalo, M. A. R., Heck, L. C., Matsuo, F. S., Mota, R. F., et al. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00065.2019 · Cited by 9 · see citing works
Zhang, H., Wang, D.-S., Wu, S.-H., Huang, G., Chen, D.-H., Ma, H., Zhang, Y.-T., Guo, L.-H., Liu, R.-Q., Gui, Z.-H., et al. (2023) · International Journal of Hygiene and Environmental Health · doi:10.1016/j.ijheh.2023.114258 · Cited by 9 · see citing works
Adipose tissue growth and development: the modulating role of ambient temperature
Symonds, M. E., Pope, M., Bloor, I. D., Law, J., Alagal, R. I., & Budge, H. (2020) · Journal of Endocrinology · doi:10.1530/joe-20-0075 · Cited by 9 · see citing works
“There are increasing indications from animal studies that brown and beige cells could be activated through individual nutrients such as capsaicin analogues (Darre & Domene 2015, Derbenev & Zsombok 2016).”
BackgroundReply to ‘Confounding issues in the ‘humanized’ brown fat of mice’
de Jong, J. M. A., Cannon, B., Nedergaard, J., Wolfrum, C., & Petrovič, N. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0193-x · Cited by 9 · see citing works
Qimuge, N., Lindsund, E., Bokhari, M. H., Pang, W., & Petrovič, N. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.105760 · Cited by 8 · see citing works
Sun, Q., Cui, X., Yin, D., Li, J., Li, J., & Du, L. (2025) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-025-01090-x · Cited by 8 · see citing works
“At thermoneutrality (30 °C), the morphology and gene expression profile of murine classical brown adipose tissue more closely resemble those of human brown adipose tissue, whereas beige adipose tissue significantly dimin - ishes its thermogenic potential under these conditions [142].”
Tóth, B. B., Barta, Z., Barta, Á. B., & Fésüs, L. (2021) · BMC Genomics · doi:10.1186/s12864-021-08126-8 · Cited by 6 · see citing works
Li, M., & Speakman, J. R. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2087-8_15 · Cited by 8 · see citing works
Regulatory networks determining substrate utilization in brown adipocytes
Onogi, Y., & Ussar, S. (2022) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2022.04.001 · Cited by 8 · see citing works
Tóth, B. B., Arianti, R., Shaw, A., Vámos, A., Veréb, Z., Póliska, S., Győry, F., Bacsó, Z., Fésüs, L., & Kristóf, E. (2020) · Cells · doi:10.3390/cells9040987 · Cited by 8 · see citing works
Supraclavicular brown adipocytes originate from Tbx1+ myoprogenitors
Huang, Z., Gu, C., Zhang, Z., Arianti, R., Swaminathan, A., Tran, K., Battist, A., Kristóf, E., & Ruan, H. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3002413 · Cited by 8 · see citing works
Lai, M., Zhou, W., Zou, W., Qiu, L., Liang, Z., Chen, W., Wang, Y., Guo, B., Zhao, C., Zhang, Z., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60474-1 · Cited by 7 · see citing works
“Meanwhile, long-term exposure to thermoneutral temperatures leads to BAT remodeling, characterized by loss of function, lipid accumulation, and diminished mitochondrial quality 35,36 .”
Boulet, N., Luijten, I. H. N., Cannon, B., & Nedergaard, J. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00352.2020 · Cited by 7 · see citing works
Beige or brite adipocytes of the adipose organ: Link with white and brown adipocytes
Amri, E. (2024) · Annales d Endocrinologie · doi:10.1016/j.ando.2024.05.002 · Cited by 7 · see citing works
Xiang, X., Liu, Y., Zeng, Z., Zhao, X., Shi, Q., Huang, X., Yang, H., Song, C., Xu, S., & Jin, S. (2025) · Journal of Functional Foods · doi:10.1016/j.jff.2025.106675 · Cited by 7 · see citing works
Innervation of supraclavicular adipose tissue: A human cadaveric study
Sievers, W., Rathner, J. A., Green, R. A., Kettle, C., Irving, H. R., Whelan, D. R., Fernandez, R. G. D., & Zacharias, A. (2020) · PLoS ONE · doi:10.1371/journal.pone.0236286 · Cited by 7 · see citing works
“The comparatively smaller cell size supports the contention that the supraclavicular adipocytes are BATlike [35].”
InfluentialStable Isotope Tracing and Metabolomics to Study In Vivo Brown Adipose Tissue Metabolic Fluxes
Jung, S. M., Le, J., Doxsey, W. G., Haley, J. D., Park, G. S. H., Guertin, D. A., & Jang, C. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2087-8_8 · Cited by 7 · see citing works
Zhao, L., Zhu, Q., Li, M., Yang, H., & Zhao, Y. (2025) · The Journal of Physiology · doi:10.1113/jp289263 · Cited by 6 · see citing works
“In mice exposed to thermoneutral conditions, BAT resembles characteristics of white adipocytes (Cui et al., 2016; de Jong et al., 2019; Fischer et al., 2020; Shi et al., 2021).”
Distinct precursor landscape of subcutaneous and visceral fat in development and aging
Lin, F., & Sul, H. S. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116706 · Cited by 7 · see citing works
“23 It has also been described that diminished adipogenic capacity and thus hypertrophy of VAT may be a dominant mechanism underlying insulin resistance in obesity.”
Isolation and Characterization of Human Brown Adipocytes
Scheele, C. C., Henriksen, T. I., & Nielsen, S. J. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2087-8_14 · Cited by 5 · see citing works
Repeated short excursions from thermoneutrality suffice to restructure brown adipose tissue
Davies, V. S., Lindsund, E., Petrovič, N., Cannon, B., & Nedergaard, J. (2023) · Biochimie · doi:10.1016/j.biochi.2023.01.006 · Cited by 5 · see citing works
Cheng, C., Wu, B., Zhang, L., Wan, Q., Peng, H., Liu, X., Zheng, H., Zhang, H., & Zou, C. (2023) · Magnetic Resonance Materials in Physics Biology and Medicine · doi:10.1007/s10334-023-01133-8 · Cited by 4 · see citing works
“Recent studies have shown that human BAT is pheno-copied by classical BAT in physiologically humanized mice [34].”
Sun, W. (2021) · Science · doi:10.1126/science.abm8138 · Cited by 4 · see citing works
CFTR regulates brown adipocyte thermogenesis via the cAMP/PKA signaling pathway
Choi, K.-M., Cho, S.-H., Kim, J. H., Kim, A.-R. L., Kong, X., & Yoon, J. C. (2022) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2022.08.012 · Cited by 4 · see citing works
“Both humans and mice possess constitutively active and inducible thermogenic fat [48,49], and recent data have highlighted the importance of human BAT in metabolic health [26].”
BackgroundPurinergic adipocyte-macrophage crosstalk promotes degeneration of thermogenic brown adipose tissue
Jaeckstein, M. Y., Fischer, A. W., Rissiek, B., Stähler, T., Heine, M., Behrens, J., Mann, O., Pfeifer, A., Magnus, T., Schlein, C., et al. (2025) · EMBO Reports · doi:10.1038/s44319-025-00642-y · Cited by 3 · see citing works
“…in extensive lipid accumulation, loss of mitochondria and thermogenic proteins such as UCP1, activation of in fl ammatory pathways and a higher abundance of pro-in fl ammatory immune cells including macrophages (de Jong et al, 2019; Fischer et al, 2020b; Kotzbeck et al, 2018; Schlein et al, 2021).”
InfluentialBatokine in Central Nervous System Diseases
Shen, M., Zhang, M., Mao, N., & Lin, Z. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03490-w · Cited by 3 · see citing works
“However, the gene expression profile of BAT in humans is highly similar to classical rodent BAT, and both exert a profound and similar effects on systemic metabolism [2, 12, 13].”
Background
- 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 › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › 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
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.
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