Cited by 530Adipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic DiseasesCardiovascular Disease and Adiposity

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Mapping of human brown adipose tissue in lean and obese young men

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Leitner, Brooks P., Huang, Shan, Brychta, Robert J., Duckworth, Courtney J., Baskin, Alison S., McGehee, Suzanne, Tal, Ilan, Dieckmann, William, Gupta, Garima, Kolodny, Gerald M., Pacak, Karel, Herscovitch, Peter, Cypess, Aaron M., Chen, Kong Y.·2017·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1705287114PMC PMC5559032

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Abstract

F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1-71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT-cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal-with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots in the upper torso. These nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat mass), and up to 90% of each depot could be activated BAT. The amount and activity of BAT was significantly influenced by region of interest selection methods, PET threshold criteria, and PET resolutions. The present study suggests that active BAT can be found in specific adipose depots in adult humans, but less than one-half of the fat in these depots is stimulated by acute cold exposure, demonstrating a previously underappreciated thermogenic potential.

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CANNON, B., & NEDERGAARD, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00015.2003 · Cited by 6,433
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Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human
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Brown adipose tissue activity controls triglyceride clearance
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“In rodent studies, BAT can have an enormous impact on energy expenditure (35) and fuel substrate consumption (36).”
Background
Partial-Volume Effect in PET Tumor Imaging
Soret, M., Bacharach, S. L., & Buvat, I. (2007) · Journal of Nuclear Medicine · doi:10.2967/jnumed.106.035774 · Cited by 1,597
Adipose tissue browning and metabolic health
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Activation of Human Brown Adipose Tissue by a β3-Adrenergic Receptor Agonist
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Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans
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Items 101–200 of 526

Obesity Tissue: Composition, Energy Expenditure, and Energy Content in Adult Humans
Hwaung, P., Bosy‐Westphal, A., Müller, M. J., Geisler, C., Heo, M., Thomas, D. M., Kennedy, S., & Heymsfield, S. B. (2019) · Obesity · doi:10.1002/oby.22557 · Cited by 42
“Similarly, we did not build brown fat, a potential source of thermogenesis, into our models (36).”
Background
Metabolic determinants of Alzheimer’s disease: A focus on thermoregulation
Tournissac, M., Leclerc, M., Valentin‐Escalera, J., Vandal, M., Bosoi, C. R., Planel, E., & Calon, F. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101462 · Cited by 41
Endothelial cell crosstalk improves browning but hinders white adipocyte maturation in 3D engineered adipose tissue
Hammel, J. H., & Bellas, E. (2020) · Integrative Biology · doi:10.1093/intbio/zyaa006 · Cited by 41
“exist primarily within infants to regulate non-shivering thermogenesis, but recently has been found in adults [18, 19].”
Background
Roles of estrogens, estrogen-like compounds, and endocrine disruptors in adipocytes
Lizcano, F. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.921504 · Cited by 47
“BAT can be stimulated in adults and could have a relevant role in the treatment of obesity (45, 46).”
Background
Brown adipose tissue-derived metabolites and their role in regulating metabolism
Ziqubu, K., Dludla, P. V., Mabhida, S. E., Jack, B. U., Keipert, S., Jastroch, M., & Mazibuko-Mbeje, S. E. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155709 · Cited by 45
Obesity‐induced tissue alterations resist weight loss: A mechanistic review
Guardia, L. D., & Shin, A. C. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15637 · Cited by 45
“18 As an example, obese individuals typically exhibit less activation of BAT compared to lean individuals, 47 and those with higher BAT deposits exhibit lower body weight than their BAT-deficient counterparts.”
Sex differences in brown adipose tissue activity and cold-induced thermogenesis
Herz, C. T., Kulterer, O. C., Prager, M., Marculescu, R., Langer, F. B., Prager, G., Kautzky‐Willer, A., Haug, A. R., & Kiefer, F. W. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111365 · Cited by 40
Metformin reduces macrophage HIF1α-dependent proinflammatory signaling to restore brown adipocyte function in vitro
Pescador, N., Francisco, V., Vázquez, P., Esquinas-Román, E. M., González-Paramos, C., Valdecantos, M. P., García‐Martinez, I., Urrutia, A. A., Ruíz-Cañas, L., Escalona-Garrido, C., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102171 · Cited by 39
“Altogether, these seminal studies suggest that a decrease in active BAT may be associated with the accumulation of visceral WAT and unfavorable metabolic parameters [10,11].”
What is obesity?
Dhurandhar, N. V. (2022) · International Journal of Obesity · doi:10.1038/s41366-022-01088-1 · Cited by 45
“For example, active thermogenic adipose tissue is more in individuals who are lean and less in obesity [7].”
Background
Do estrogens enhance activation of brown and beiging of adipose tissues?
Frank, A. P., Palmer, B. F., & Clegg, D. J. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.09.026 · Cited by 37
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Hropot, T., Herman, R., Janez, A., Lezaic, L., & Jensterle, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108592 · Cited by 39
“Accordingly, in addition to increasing energy expenditure, BAT activation could potentially improve certain metabolic parameters (hyperglycemia, dyslipidemia), making BAT activation a potential therapeutic target for obesity and other metabolic diseases [16,28].”
Background
Adipose Tissue Development Relies on Coordinated Extracellular Matrix Remodeling, Angiogenesis, and Adipogenesis
Johnston, E. K., & Abbott, R. D. (2022) · Biomedicines · doi:10.3390/biomedicines10092227 · Cited by 45
“5% of the adult human mass and is replaced by white adipose tissue as the primary adipose mass [9,10].”
Background
Hypoxia signaling in the adipose tissue
Huynh, P. M., Wang, F., & An, Y. (2024) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjae039 · Cited by 42
“By contrast, BAT accounts for a small portion of total AT ( ∼ 4.3% of fat mass in men); its primary function is dissipating lipids as heat to protect mammals from hypothermia during cold exposure or β -adrenergic stimulations (Leitner et al., 2017 ; Koenen et al., 2021 ).”
Influential
miR-199a-3p regulates brown adipocyte differentiation through mTOR signaling pathway
Gao, Y., Cao, Y., Cui, X., Wang, X., Zhou, Y., Huang, F., Wang, X., Wen, J., Xie, K., Xu, P., et al. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2018.05.005 · Cited by 37
mTOR signaling in Brown and Beige adipocytes: implications for thermogenesis and obesity
Ye, Y., Liu, H., Zhang, F., & Hu, F. (2019) · Nutrition & Metabolism · doi:10.1186/s12986-019-0404-1 · Cited by 39
Impact of pesticide exposure on adipose tissue development and function
Gutgesell, R. M., Tsakiridis, E. E., Jamshed, S., Steinberg, G. R., & Holloway, A. C. (2020) · Biochemical Journal · doi:10.1042/bcj20200324 · Cited by 40
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 38
“It has been estimated that adult lean men may have around 330ml of cold-inducible BAT, with lower volumes (around 130ml) found in obese men (18).”
Background
PGE2‐EP3 axis promotes brown adipose tissue formation through stabilization of WTAP RNA methyltransferase
Tao, X., Du, R., Guo, S., Feng, X., Yu, T., Ouyang, Q., Chen, Q., Fan, X., Wang, X., Guo, C., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2021110439 · Cited by 38
“Accumulated evidence has shown that functionally active BAT deposits are observed in the cervical – supraclavicular, paravertebral, and mediastinal regions of adult humans (Leitner et al , 2017; Becher et al , 2021).”
Fatty infiltration in the musculoskeletal system: pathological mechanisms and clinical implications
Zhu, Y., Hu, Y., Pan, Y., Li, M., Niu, Y., Zhang, T., Sun, H., Zhou, S., Liu, M., Zhang, Y., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1406046 · Cited by 44
“BAT is composed of multiple smaller lipid droplets distributed in certain anatomical depots in the neck, posterior thorax, shoulders, and abdomen, with high vascularization and high mitochondrial levels (4).”
Background
Brown and beige fat: From molecules to physiology
Chondronikola, M., & Sidossis, L. S. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2018.05.014 · Cited by 38
Activation of brown adipose tissue enhances the efficacy of caloric restriction for treatment of nonalcoholic steatohepatitis
Poekes, L., Gillard, J., Farrell, G. C., Horsmans, Y., & Leclercq, I. A. (2018) · Laboratory Investigation · doi:10.1038/s41374-018-0120-x · Cited by 38
Recent advances in our understanding of brown and beige adipose tissue: the good fat that keeps you healthy
Symonds, M. E., Aldiss, P., Pope, M., & Budge, H. (2018) · F1000Research · doi:10.12688/f1000research.14585.1 · Cited by 35
The good and the BAT of metabolic sex differences in thermogenic human adipose tissue
Keuper, M., & Jastroch, M. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111337 · Cited by 39
“60–94% in BAT-positive individuals (Lee et al., 2010; Leitner et al., 2017; Ouellet et al., 2011; Persichetti et al., 2013).”
Background
The impact of adipokines on vascular networks in adipose tissue
Vliora, M., Ravelli, C., Grillo, E., Corsini, M., Flouris, A. D., & Mitola, S. M. F. (2022) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2022.07.008 · Cited by 37
Obesity and Adipose-Derived Extracellular Vesicles: Implications for Metabolic Regulation and Disease
Malaguarnera, M., Cauli, O., & Cabrera‐Pastor, A. (2025) · Biomolecules · doi:10.3390/biom15020231 · Cited by 39
“BAT is typically reduced in individuals who are obese or elderly and is also associated with cardiovascular health [21,22].”
Genetic Markers of Brown Adipose Tissue Identity and In Vitro Brown Adipose Tissue Activity in Humans
Nascimento, E. B. M., Sparks, L. M., Divoux, A., van Gisbergen, M. W., Broeders, E. P. M., Jörgensen, J. A., Schaart, G., Bouvy, N. D., Lichtenbelt, W. D. V. M., & Schrauwen, P. (2017) · Obesity · doi:10.1002/oby.22062 · Cited by 37
“However, the current topic of debate questions whether we fully grasp the complete thermogenic potential of active human BAT (22).”
Background
The Regulation of Lipokines by Environmental Factors
Hernández‐Saavedra, D., & Stanford, K. I. (2019) · Nutrients · doi:10.3390/nu11102422 · Cited by 34
Accurate quantification of brown adipose tissue mass by xenon-enhanced computed tomography
Branca, R. T., McCallister, A., Yuan, H., Aghajanian, A., Faber, J. E., Weimer, N. E., Buchanan, R., Floyd, C. S., Antonacci, M., Zhang, L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714431115 · Cited by 34
“Discussion After >8 y of renewed interest in BAT, the functional relevance of BAT in humans is still largely undetermined, as estimations of BAT volume have ranged from a meager 14 g (14) to >500 g (5, 7, 13).”
Background
Extracellular Vesicles in Adipose Tissue Communication with the Healthy and Pathological Heart
Michel, L. Y. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24097745 · Cited by 36
“and supraclavicular regions in 3–7% of adults [8,9], and tend to be reduced in obese and elderly subjects [8,10].”
Background
Defective extracellular matrix remodeling in brown adipose tissue is associated with fibro-inflammation and reduced diet-induced thermogenesis
Pellegrinelli, V., Figueroa‐Juárez, E., Samuelson, I., U-Din, M., Rodríguez‐Fdez, S., Virtue, S., Leggat, J., Çubuk, C., Peirce, V. J., Niemi, T. S., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112640 · Cited by 37
Association of objectively measured physical activity with brown adipose tissue volume and activity in young adults
Acosta, F. M., Martínez‐Téllez, B., Sánchez‐Delgado, G., Migueles, J. H., Contreras-Gomez, M. A., Martinez-Avila, W. D., Merchán-Ramírez, E., Alcántara, J. M. A., Amaro‐Gahete, F. J., Elvira, J. M. L., et al. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01312 · Cited by 32
“With this purpose, we outlined six regions of interest (ROIs), from atlas vertebrae to thoracic vertebrae 4, using a three-dimensional axial technique (39).”
Method
Functional characterization of human brown adipose tissue metabolism
Richard, M. A., Pallubinsky, H., & Blondin, D. P. (2020) · Biochemical Journal · doi:10.1042/bcj20190464 · Cited by 31
Thermogenic adipose tissue aging: Mechanisms and implications
Silva, G. D. N., & Amato, A. A. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.955612 · Cited by 39
“In adults, thermogenic adipose tissue is detected in the cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal (including subcutaneous) regions (Leitner et al., 2017), more frequently in women than men, and declines progressively with age (Cypess et al.”
Background
Exercise-induced regulation of adipose tissue
Stroh, A. M., & Stanford, K. I. (2023) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2023.102058 · Cited by 33
An Update on the Role and Potential Molecules in Relation to Ruminococcus gnavus in Inflammatory Bowel Disease, Obesity and Diabetes Mellitus
Hong, J., Fu, T., Liu, W., Du, Y., Bu, J., Wei, G., Yu, M., Lin, Y., Min, C., & Lin, D. (2024) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s456173 · Cited by 33
“138,139 GUDCA has the ability to regulate bile acid metabolism and induce the production of taurolithocholic acid (TLCA), as well as activate the g-protein-coupled bile acid receptor (GPBAR)-1 and UCP1.”
Background
Pheochromocytoma and Paraganglioma Patients With Poor Survival Often Show Brown Adipose Tissue Activation
Sater, Z. A., Jha, A., Hamimi, A., Mandl, A., Hartley, I. R., Gubbi, S., Patel, M. A., Gonzales, M., Taïeb, D., Civelek, A. C., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz314 · Cited by 31
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 31
The gut hormone secretin triggers a gut–brown fat–brain axis in the control of food intake
Schnabl, K., Li, Y., & Klingenspor, M. (2020) · Experimental Physiology · doi:10.1113/ep087878 · Cited by 31
“, 2016); BATmass (Leitner et al., 2017); 20 kJ (l O2) −1 (Leonard, 2010); AT density 0.”
White and beige adipocytes: are they metabolically distinct?
Sepa-Kishi, D. M., & Ceddia, R. B. (2018) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2018-0003 · Cited by 31
Brown adipose tissue and lipid metabolism: New strategies for identification of activators and biomarkers with clinical potential
Xiang, A. S., Meikle, P. J., Carey, A. L., & Kingwell, B. A. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.07.002 · Cited by 29
Laminins in metabolic tissues
GODDI, A. A., Schroedl, L. M., Brey, E. M., & Cohen, R. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154775 · Cited by 33
Mitochondrial dysfunction plays an essential role in remodeling aging adipose tissue
Macêdo, A. P. A., da Silva, A. S. R., Muñoz, V. R., Ropelle, E. R., & Pauli, J. R. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111598 · Cited by 30
Brown and beige adipose tissue: New therapeutic targets for metabolic disorders
Magro, B. S., & Dias, D. P. M. (2024) · Health Sciences Review · doi:10.1016/j.hsr.2024.100148 · Cited by 34
Optogenetic‐induced sympathetic neuromodulation of brown adipose tissue thermogenesis
Lyons, C. E., Razzoli, M., Larson, E. B., Svedberg, D. A., Frontini, A., Cinti, S., Vulchanova, L., Sanders, M. A., Thomas, M. J., & Bartolomucci, A. (2019) · The FASEB Journal · doi:10.1096/fj.201901361rr · Cited by 29
The Sick Adipose Tissue: New Insights Into Defective Signaling and Crosstalk With the Myocardium
Bermúdez, V., Durán, P., Rojas, E., Diaz, M. P., Rivas, J., Nava, M., Chacín, M., de Bravo, M. C., Carrasquero, R., Ponce, C. C., et al. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.735070 · Cited by 31
Adipose tissue: colors, depots and functions
Romantsova, T. I. (2021) · Obesity and metabolism · doi:10.14341/omet12748 · Cited by 31
Cardiometabolic implications of adipose tissue aging
Ahmed, B., Farb, M. G., & Gokce, N. (2024) · Obesity Reviews · doi:10.1111/obr.13806 · Cited by 32
“17 When body adiposity falls below levels of 3 – 5% for men and 8 – 12% for women, homeostatic functions can be disrupted.”
ASC‐1 transporter‐dependent amino acid uptake is required for the efficient thermogenic response of human adipocytes to adrenergic stimulation
Arianti, R., Vinnai, B. Á., Tóth, B. B., Shaw, A., Csősz, É., Vámos, A., Győry, F., Fischer‐Posovszky, P., Wabitsch, M., Kristóf, E., et al. (2021) · FEBS Letters · doi:10.1002/1873-3468.14155 · Cited by 28
The evolutionary significance of human brown adipose tissue: Integrating the timescales of adaptation
Lévy, S., & Leonard, W. R. (2021) · Evolutionary Anthropology Issues News and Reviews · doi:10.1002/evan.21930 · Cited by 28
“document higher estimates of BAT volume and metabolic activity.(17,27,64)”
Background
Brown adipose tissue and glucose homeostasis – the link between climate change and the global rise in obesity and diabetes
Symonds, M. E., Farhat, G., Aldiss, P., Pope, M., & Budge, H. (2018) · Adipocyte · doi:10.1080/21623945.2018.1551689 · Cited by 28
“rent imaging techniques and the difficulty in measurement because of the mixing of brown and beige fat with other white fat depots inmultiple sites in the body.(19) Beige fat is defined as being a discrete region within white fat that possesses UCP1 although at approximately ten-fold lower concentrations than “classic…”
BackgroundMethodInfluential
Central vs. Peripheral Action of Thyroid Hormone in Adaptive Thermogenesis: A Burning Topic
Zekri, Y., Flamant, F., & Gauthier, K. (2021) · Cells · doi:10.3390/cells10061327 · Cited by 27
“In adults, browning can take place under certain conditions within specific WAT depots, particularly in the abdominal, paraspinal, supraclavicular and cervical regions [35].”
Background
Medicinal and edible polysaccharides from ancient plants: extraction, isolation, purification, structure, biological activity and market trends of sea buckthorn polysaccharides
Xu, X., Liu, X., Yu, S., Wang, T., Li, R., Zhang, Y., & Liu, Y. (2024) · Food & Function · doi:10.1039/d3fo04140a · Cited by 27
Intercellular and inter-organ crosstalk in browning of white adipose tissue: molecular mechanism and therapeutic complications
Cheong, L. Y., & Xu, A. (2021) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjab038 · Cited by 28
“cold exposure seems to promote a wider distribution of glucose uptake in AT than previously identified BAT regions in adult humans (Leitner et al., 2017).”
BackgroundInfluential
The thermoneutral zone in women takes an “arctic” shift compared to men
Brychta, R. J., McGehee, S., Huang, S., Leitner, B. P., Duckworth, C. J., Fletcher, L. A., Kim, K., Cassimatis, T. M., Israni, N. S., Lea, H. J., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2311116121 · Cited by 30
Human brown adipose tissue is not enough to combat cardiometabolic diseases
Carpentier, A. C., & Blondin, D. P. (2023) · Journal of Clinical Investigation · doi:10.1172/jci175288 · Cited by 28
“Radiological mapping of adipose tissue depots containing 18 FDG-positive BAT suggests upper ranges of 550 to 2550 mL, although only a small fraction of these volumes is demon-strably active metabolically (11).”
Adipose Tissue Composition in Obesity and After Bariatric Surgery
Adami, G. F., Carbone, F., Montecucco, F., Camerini, G. B., & Cordera, R. (2019) · Obesity Surgery · doi:10.1007/s11695-019-04030-z · Cited by 26
Omega-3 fatty acids as regulators of brown/beige adipose tissue: from mechanisms to therapeutic potential
Fernández‐Galilea, M., Félix‐Soriano, E., Colón-Mesa, I., Escoté, X., & Moreno-Aliaga, M. J. (2019) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-019-00720-5 · Cited by 27
“During obesity onset, as long as WAT mass increases BAT activity decreases [54].”
Background
ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue
Sebag, S. C., Zhang, Z., Qian, Q., Li, M., Zhu, Z., Harata, M., Li, W., Zingman, L. V., Liu, L., Lira, V. A., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110003 · Cited by 28
“BAT ADH5 protects against obesity-associated metabolic dysfunction Obesity suppresses BAT metabolic function (Blondin et al., 2015; Himms-Hagen, 1985; Leitner et al., 2017; Shimizu et al., 2014; Shimizu and Walsh, 2015) and increases immune cell infiltration and ROS production (Alcalá et al.”
The Adipose Tissue Macrophages Central to Adaptive Thermoregulation
Rahman, M. S., & Jun, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.884126 · Cited by 32
“So far, adult humans have been known to have thermogenic fat in several anatomic areas, including cervical, axillary, paraspinal, mediastinal, and abdominal, as well as supraclavicular (24).”
Background
Brown adipose tissue is not associated with cachexia or increased mortality in a retrospective study of patients with cancer
Eljalby, M., Huang, X., Becher, T., Wibmer, A. G., Jiang, C. S., VAUGHAN, R. D., Schöder, H. M., & Cohen, P. (2022) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00187.2022 · Cited by 26
Kinetics of human brown adipose tissue activation and deactivation
Leitner, B. P., Weiner, L. S., Desir, M., Kahn, P. A., Selen, D. J., Tsang, C., Kolodny, G. M., & Cypess, A. M. (2018) · International Journal of Obesity · doi:10.1038/s41366-018-0104-3 · Cited by 28
“well with total-body BAT metabolic activity [18].”
The Sympathetic Innervation of Adipose Tissues: Regulation, Functions, and Plasticity
Willows, J. W., Blaszkiewicz, M., & Townsend, K. L. (2023) · Comprehensive physiology · doi:10.1002/cphy.c220030 · Cited by 46
“Human BAT, while occupying proportionally less volume relative to rodent BAT, is activated by cold exposure as identified by PET/CT imaging, UCP1 expression, and increased energy expenditure (67, 152, 190, 284, 296).”
Transcriptional Factors of Thermogenic Adipocyte Development and Generation of Brown and Beige Adipocytes From Stem Cells
Nguyen, T.-T. V., Vu, V. V., & Pham, P. V. (2020) · Stem Cell Reviews and Reports · doi:10.1007/s12015-020-10013-w · Cited by 25
The Transcriptional Role of Vitamin A and the Retinoid Axis in Brown Fat Function
Herz, C. T., & Kiefer, F. W. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00608 · Cited by 27
“Cold-induced BAT activity is mainly found in deep cervical, supraclavicular, paraaortal, and some renal fat depots in human adults (15).”
Background
The Adipokine Component in the Molecular Regulation of Cancer Cell Survival, Proliferation and Metastasis
Umar, M. I., Hassan, W., Murtaza, G., Buabeid, M. A., Arafa, E. A., Irfan, H. M., Asmawi, M. Z., & Huang, X. (2021) · Pathology & Oncology Research · doi:10.3389/pore.2021.1609828 · Cited by 25
“Previously, BAT was believed to exist in neonates exclusively, it is only recently that the anatomical location of BAT is reported in the axillary, perivascular, perirenal, cervical and supraclavicular regions in adults [3].”
Background
Influence of Polyphenols on Adipose Tissue: Sirtuins as Pivotal Players in the Browning Process
Flori, L., Piragine, E., Spezzini, J., Citi, V., Calderone, V., & Martelli, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119276 · Cited by 30
Adaptive thermogenesis enhances the life-threatening response to heat in mice with an Ryr1 mutation
Wang, H. J., Lee, C. S., Yee, R. S. Z., Groom, L. A., Friedman, I., Babcock, L. W., Georgiou, D. K., Hong, J., Hanna, A. D., Recio, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18865-z · Cited by 26
Brown Adipose Tissue: A Metabolic Regulator in a Hypothalamic Cross Talk?
Henningsen, J. B., & Schéele, C. (2020) · Annual Review of Physiology · doi:10.1146/annurev-physiol-032420-042950 · Cited by 24
Mitochondrial dynamics keep balance of nutrient combustion in thermogenic adipocytes
Michurina, S. S., Stafeev, I., Menshikov, M. Y., & Parfyonova, Y. V. (2021) · Mitochondrion · doi:10.1016/j.mito.2021.05.001 · Cited by 26
Infrared Thermography
Law, J., Morris, D. E., Budge, H., & Symonds, M. E. (2018) · Handbook of experimental pharmacology · doi:10.1007/164_2018_137 · Cited by 25
Functional ingredients present in whole-grain foods as therapeutic tools to counteract obesity: Effects on brown and white adipose tissues
Zhang, K., Sun, J., Fan, M., Qian, H., Ying, H., Li, Y., & Wang, L. (2021) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2021.01.055 · Cited by 24
LncRNA Ctcflos orchestrates transcription and alternative splicing in thermogenic adipogenesis
Bast‐Habersbrunner, A., Kiefer, C., Weber, P., Fromme, T., Schießl, A., Schwalie, P. C., Deplancke, B., Li, Y., & Klingenspor, M. (2021) · EMBO Reports · doi:10.15252/embr.202051289 · Cited by 21
“Mapping of cold-inducible brown and brite adipocytes in lean and obese humans revealed a previously underestimated potential for the recruitment of thermogenic adipocytes in non-subcutaneous adipose tissue depots (Leitner et al, 2017).”
Mouse model of the adipose organ: the heterogeneous anatomical characteristics
Chun, K. (2021) · Archives of Pharmacal Research · doi:10.1007/s12272-021-01350-6 · Cited by 27
Defective brown adipose tissue thermogenesis and impaired glucose metabolism in mice lacking Letmd1
Choi, K.-M., Kim, J. H., Kong, X., Isik, M., Zhang, J., Lim, H., & Yoon, J. C. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110104 · Cited by 25
“Recent data indicate that adult humans possess more extensive cold-activated thermogenic adipose tissue than previously estimated (Cypess et al., 2009; Leitner et al., 2017; van Marken Lichtenbelt et al., 2009; Virtanen et al., 2009).”
Exercise-Induced Adipose Tissue Thermogenesis and Browning: How to Explain the Conflicting Findings?
Zhu, Y., Qi, Z., & Ding, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113142 · Cited by 27
“However, functional BAT is still present in adults (such as supraclavicular, neck, vertebral side, mediastinum and kidney) [2].”
Background
An obesogenic diet impairs uncoupled substrate oxidation and promotes whitening of the brown adipose tissue in rats
Eira, D. D., Jani, S., & Ceddia, R. B. (2022) · The Journal of Physiology · doi:10.1113/jp283721 · Cited by 24
“In fact, it has been reported that after 5 h of tolerable cold exposure (16°C), activated BAT in obese men corresponded to only ∼39% of that of lean counterparts, even though the total volume of BAT-containing depots was almost two-fold higher in the former than the latter group of subjects (Leitner et al., 2017).”
BackgroundResultInfluential
Revisiting adipose thermogenesis for delaying aging and age-related diseases: Opportunities and challenges
Tarantini, S., Subramanian, M., Butcher, J. T., Yabluchanskiy, A., Li, X., Miller, R. A., & Balasubramanian, P. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101912 · Cited by 24
Characterization of brown adipose tissue (BAT) in polycystic ovary syndrome (PCOS) patients by Z-Spectral Imaging (ZSI)
Li, L., Scotti, A., Fang, J., Li, Y., Xiong, T., He, W., Qin, Y., Liew, C. W., Khayyat, N., Zhu, W., et al. (2019) · European Journal of Radiology · doi:10.1016/j.ejrad.2019.108777 · Cited by 23
The Remaining Mysteries about Brown Adipose Tissues
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Chronic Intermittent Hypoxia during Sleep Causes Browning of Interscapular Adipose Tissue Accompanied by Local Insulin Resistance in Mice
Dahan, T., Nassar, S., Yajuk, O., Steinberg, E., Benny, O., Abudi, N., Plaschkes, I., Benyamini, H., Gozal, D., Abramovitch, R., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415462 · Cited by 24
“In recent years, BAT has gained a renewed interest with the unequivocal demonstration of active and dynamic depots in human adults and its role in insulin sensitivity in humans [27,39,40].”
Background
Techniques and Applications of Magnetic Resonance Imaging for Studying Brown Adipose Tissue Morphometry and Function
Karampinos, D. C., Weidlich, D., Wu, M., Hu, P., & Franz, D. (2018) · Handbook of experimental pharmacology · doi:10.1007/164_2018_158 · Cited by 22
BMP7 Increases UCP1-Dependent and Independent Thermogenesis with a Unique Gene Expression Program in Human Neck Area Derived Adipocytes
Shaw, A., Tóth, B. B., Arianti, R., Csomós, I., Póliska, S., Vámos, A., Bacsó, Z., Győry, F., Fésüs, L., & Kristóf, E. (2021) · Pharmaceuticals · doi:10.3390/ph14111078 · Cited by 23
“Healthy human adults possess thermogenic brown adipose tissue (BAT) that can dissipate energy as heat under sub-thermal conditions [1,2].”
Background
Dietary succinate supplementation to maternal mice improves fetal brown adipose tissue development and thermogenesis of female offspring
Liu, X., Chen, Y., Zhao, L., Tian, Q., de Avila, J. M., Zhu, M. J., & Du, ‬. (2021) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2021.108908 · Cited by 23
Brown adipocytes from induced pluripotent stem cells—how far have we come?
Brown, A. C. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14257 · Cited by 22
The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ crosstalk
Valdecantos, M. P., Ruiz, L., Folgueira, C., Rada, P., Gómez‐Santos, B., Solas, M., Hitos, A. B., Field, J., Francisco, V., Escalona-Garrido, C., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54080-w · Cited by 24
“In this regard, Leitner et al. 41 have recently repor-ted a human “ BATlas ” in lean and obese individuals revealing that obese men have substantial quantities of “ brownable ” fat in different depots including those with abdominal location that may have a greater potential for expansion upon an…”
Reduced brown adipose tissue activity during cold exposure is a metabolic feature of the human thrifty phenotype
Hollstein, T., Vinales, K. L., Chen, K. Y., Cypess, A. M., Basolo, A., Schlögl, M., Krakoff, J. A., & Piaggi, P. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154709 · Cited by 20
“BAT is primarily localized in the cervical-supraclavicular region[10] although it is also detectable in the axillary, mediastinal, paraspinal, and abdominal regions[37, 38].”
Background
Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour
Álvarez-Artime, A., García-Soler, B., Sainz, R. M., & Mayo, J. C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115560 · Cited by 24
“Nevertheless, very recently, Leitner and co-workers have accurately mapped the human BAT depots, using positron emission tomography/computed tomography, showing that previous studies have underestimated the presence of this tissue in adults [8].”
Background
The human batokine EPDR1 regulates β-cell metabolism and function
Cataldo, L. R., Gao, Q., Argemi‐Muntadas, L., Hodek, O., Cowan, E., Hladkou, S., Gheibi, S., Spégel, P., Prasad, R. B., Eliasson, L., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101629 · Cited by 23
“Interestingly, EPDR1 is also upregulated in BAT of obese subjects [19] and it has been shown that obese vs lean healthy subjects have elevated fat accumulation in BAT-depots [43] and pancreases [44].”
Background
The impact of metabolic endotoxaemia on the browning process in human adipocytes
Omran, F., Murphy, A. M., Younis, A. Z., Kyrou, I., Vrbíková, J., Hainer, V., Šrámková, P., Fried, M., Ball, G., Tripathi, G., et al. (2023) · BMC Medicine · doi:10.1186/s12916-023-02857-z · Cited by 22
“In obesity, BAT mass/activity appears to reduce, with multiple studies indicating that individuals with obesity have reduced BAT compared with their lean counterparts [18, 21, 22].”
Background
GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity
Sun, X.-N., An, Y., Paschoal, V. A., de Souza, C. O., Wang, M.-Y., Vishvanath, L., Bueno, L. M. A., Cobb, A., Carrion, J. A. N., Ibe, M. E., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci168992 · Cited by 22
Balancing Act: Exploring the Gut Microbiota-Brown Adipose Tissue Axis in PCOS Pathogenesis and Therapeutic Frontiers
Li, Y., Fang, Y., Wang, H., & Zhang, H. (2024) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2906208 · Cited by 23
Distribution of Brown Adipose Tissue Radiodensity in Young Adults: Implications for Cold [18F]FDG-PET/CT Analyses
Martínez‐Téllez, B., Sánchez‐Delgado, G., Boon, M. R., Rensen, P. C. N., Elvira, J. M. L., & Ruiz, J. R. (2019) · Molecular Imaging and Biology · doi:10.1007/s11307-019-01381-y · Cited by 21
Molecular Regulation of Thermogenic Mechanisms in Beige Adipocytes
Yang, S., Liu, Y., Wu, X., Zhu, R., Sun, Y., Zou, S., Zhang, D., & Yang, X. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126303 · Cited by 28
“In 2009, the distribution of BAT in the supraclavicular, cervical, axillary, mediastinal, paraspinal and abdominal depots of the adult uterus has been confirmed by 18F-FDG-PET/CT [25,26].”
Background
Pyridostigmine protects against cardiomyopathy associated with adipose tissue browning and improvement of vagal activity in high-fat diet rats
Lü, Y., Wu, Q., Liu, L., Yu, X., Liu, J., Li, M., & Zang, W. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.01.006 · Cited by 22
Role of bile acid receptor FXR in development and function of brown adipose tissue
Yang, J., de Vries, H. D., Mayeuf-Louchart, A., Stroeve, J. H. M., Bloks, V. W., Koehorst, M., Duez, H., Staels, B., Kuipers, F., & van Zutphen, T. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2022.159257 · Cited by 20
Dietary fatty acids activate or deactivate brown and beige fat
Jia, M., Xu, T., Xu, Y., & Liu, Y. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121978 · Cited by 20
Semaglutide 6-months therapy of type 2 diabetes mellitus restores adipose progenitors potential to develop metabolically active adipocytes
Stafeev, I., Agareva, M. Y., Michurina, S. S., Tomilova, A., Shestakova, E. A., Zubkova, E., Sineokaya, M. S., Ratner, E. I., Menshikov, M. Y., Parfyonova, Y. V., et al. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176476 · Cited by 22
Pioglitazone does not synergize with mirabegron to increase beige fat or further improve glucose metabolism
Finlin, B. S., Memetimin, H., Zhu, B., Confides, A. L., Vekaria, H. J., Khouli, R. H. E., Johnson, Z., Westgate, P. M., Chen, J., Morris, A. J., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.143650 · Cited by 19
“Some of those studies were performed on obese research participants and found that cold induced BAT and improved metabolism (20, 22, 24, 26).”
Brown Adipose Tissue Volume and Fat Content Are Positively Associated With Whole-Body Adiposity in Young Men—Not in Women
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
What puts the heat on thermogenic fat: metabolism of fuel substrates
Sponton, C. H., Júnior, J. C. D. L., & Leiria, L. O. (2022) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2022.05.003 · Cited by 19

Authors: Leitner, B. P., Huang, S., Brychta, R. J., Duckworth, C. J., Baskin, A. S., McGehee, S., Tal, I., Dieckmann, W., Gupta, G., Kolodny, G. M., Pacak, K., Herscovitch, P., Cypess, A. M., & Chen, K. Y.
Affiliations: National Institutes of Health (US)
Beth Israel Deaconess Medical Center (US)
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
ORCID: Leitner, Brooks P.
Huang, Shan
Brychta, Robert J.
Duckworth, Courtney J.
Baskin, Alison S.
Gupta, Garima
Cypess, Aaron M.
Chen, Kong Y.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2017-07-24
Volume: 114
Issue: 32
Pages: 8649-8654
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1705287114
PMC: PMC5559032
OpenAlex: W2736913806
Cited by: 530
References: 43
Citations by year: 2026: 36 · 2025: 45 · 2024: 51 · 2023: 68 · 2022: 73 · 2021: 82 · 2020: 73 · 2019: 45 · 2018: 46 · 2017: 9
FWCI: 34.99
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.pnas.org/site/misc/userlicense.xhtml (vor)
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (Z01 DK071014, Z01 DK075116)
Topics: Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords: brown adipose tissue, obesity, cold exposure, thermogenesis, BAT activation
MeSH terms: Adult, Adipose Tissue, Brown, Humans, Male, Obesity, Tomography, X-Ray Computed, Body Mass Index, Glucose-6-Phosphate, Positron-Emission Tomography, Adiposity

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Mapping of human brown adipose tissue in lean and obese young men

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