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Brown fat as a therapy for obesity and diabetes
Open accessAbstract
PURPOSE OF REVIEW: Human fat consists of white and brown adipose tissue (WAT and BAT). Though most fat is energy-storing WAT, the thermogenic capacity of even small amounts of BAT makes it an attractive therapeutic target for inducing weight loss through energy expenditure. This review evaluates the recent discoveries regarding the identification of functional BAT in adult humans and its potential as a therapy for obesity and diabetes. RECENT FINDINGS: Over the past year, several independent research teams used a combination of positron-emission tomography and computed tomography (PET/CT) imaging, immunohistochemistry, and gene and protein expression assays to prove conclusively that adult humans have functional BAT. This has occurred against a backdrop of basic studies defining the origins of BAT, new components of its transcriptional regulation, and the role of hormones in stimulation of BAT growth and differentiation. SUMMARY: Adult humans have functional BAT, a new target for antiobesity and antidiabetes therapies focusing on increasing energy expenditure. Future studies will refine the methodologies used to measure BAT mass and activity, expand our knowledge of critical-control points in BAT regulation, and focus on testing pharmacological agents that increase BAT thermogenesis and help achieve long-lasting weight loss and an improved metabolic profile.
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“BAT is especially abundant in hibernating mammals 74 , but can also be found in adult humans 75.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [75]
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“More than a decade after the discovery of BAT as a functional and secretory tissue in adult humans, there is emerging evidence suggesting BAT as a promising therapeutic target for treating various metabolic diseases and its comorbidities (Cypess et al, 2009; Cypess and Kahn, 2010).”
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“thereby impact on plasma glucose and lipid levels, which makes them an appealing therapeutic target for the treatment of metabolic disorders (4, 5).”
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“After infancy, the major BAT depot is located in the cervical‐supraclavicular region.(1,4) Based on observations in adults, this depot likely contains brown adipocytes of both classic brown and recruitable beige origin,(5-7) intermixed with white adipose tissue (WAT) composed of white adipocytes.”
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“By contrast, BAT, rich in mitochondria, drives thermo-genesis through uncoupling protein 1 (UCP1), which dissipates energy as heat, a process essential for neonatal and cold-induced thermoregulation 10 .”
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“Literature reveals that promotion of conversion of BAT into WAT reduces the regulation of energy and develops obesity [19].”
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“Because of this hallmark, BAT has been coined an important target to combat metabolic disease [12, 13].”
BackgroundExercise as a Therapeutic Intervention
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“This type of cells are supposed to be related with non‐shivering thermogenesis, energy expenditure, and improved metabolic outcomes.(30,31) Alterations in the inflammatory gene expressions are thought to be one of the possible reasons of browning of the adipose tissue.”
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ResultBrown Adipose Tissue is Associated with Improved Cardiometabolic Health and Regulates Blood PressurePreprint
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BackgroundLoss of cAMP Signaling in CD11c Immune Cells Protects Against Diet-Induced Obesity
Zeng, L., Herdman, D. S., Lee, S. M., Tao, A., Das, M., Bertin, S., Eckmann, L., Mahata, S. K., Wu, P., Hara, M., et al. (2023) · Diabetes · doi:10.2337/db22-1035 · Cited by 9
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“In contrast, brown adipose tissue (BAT) participates in thermogenesis via uncoupling protein 1 (UCP1) and is considered metabolically protective [8].”
Recent advancements in pharmacological strategies to modulate energy balance for combating obesity
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“BAT is a specialized type of adipose tissue that plays a critical role in thermoregulation by generating heat through nonshivering thermogenesis (NST) [8].”
BackgroundBMP11 regulates thermogenesis in white and brown adipocytes
Pham, H. G., Mukherjee, S., Choi, M. J., & Yun, J. W. (2021) · Cell Biochemistry and Function · doi:10.1002/cbf.3615 · Cited by 9
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“Accord-ingly, a more recent approach to body weight reduction involves accelerating brown adipose tissue (BAT) activity by stimulating the uncoupling protein 1 (UCP1) (73).”
Inhibition of a Novel CLK1-THRAP3-PPARγ Axis Improves Insulin Sensitivity
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“…tissue (BAT) exists in adult humans (Nedergaard et al., 2007, 2010) and its characteristics of high energy expenditure (Fruhbeck et al., 2009; Cypess and Kahn, 2010; Haas et al., 2012; Heeren and Munzberg, 2013) underlie BAT’s emergence as a potential intrinsic target for prevention of…”
BackgroundAbsolute thermometry of human brown adipose tissue by magnetic resonance with laser polarized 129Xe
Zhang, L., Antonacci, M., Burant, A., McCallister, A., Kelley, M., Bryden, N. J., McHugh, C. T., Atalla, S., Holmes, L., Katz, L. M., et al. (2023) · Communications Medicine · doi:10.1038/s43856-023-00374-x · Cited by 8
“We cannot exclude that this was indeed the case for participant 14, one of the three participants that resulted BAT-negative in PET scans and in which BAT temperature was measured to be less than 38 °C.”
Adipose Tissue, Hormones, and Treatment of Type 1 Diabetes
Gunawardana, S. C. (2012) · Current Diabetes Reports · doi:10.1007/s11892-012-0300-9 · Cited by 8
“A number of reports suggest a link between the quantity of BAT and generalized leanness or decrease in obesity [80, 83, 85, 86].”
BackgroundToward noninvasive quantification of adipose tissue oxygenation with MRI
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“In the case of BAT, which plays an important role in glucose metabolism in the body [6, 8, 40], a noninvasive, nonionizing method for identification is of critical importance [8].”
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“The distinction between the energy-storing properties of WAT and the energy-spending (thermogenic) features of BAT has reciprocal implications for metabolism: WAT accumulation is linked to obesity and associated diseases, such as diabetes and hyperlipidemia, whereas BAT activation protects against these conditions.(1)…”
Challa, A. A., Vidal, P., Maurya, S. K., Maurya, C. K., Baer, L. A., Wang, Y., James, N. M., Pardeshi, P. J., Fasano, M. J., Carley, A. N., et al. (2024) · The FASEB Journal · doi:10.1096/fj.202400922r · Cited by 10
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“Although functional roles of these tissues are supposed to be directly opposite in view of obesity prevention problem (Cypess and Kahn 2010), this concept is not yet conventional (Jensen 2015) and needs further elaboration [that is also true in regard of brown fat associations with cancer (Berstein…”
BackgroundKato, H., Ario, T., Kishida, T., Manami, T., Osawa, S., Maeda, Y., Takakura, H., & Izawa, T. (2020) · Experimental Physiology · doi:10.1113/ep089114 · Cited by 7
“Rediscovery of the presence of functional BAT in humans highlights the role of active BAT in the prevention of diet-induced obesity, insulin resistance and type 2 diabetes via its thermogenic activity (Cypess & Kahn, 2010; Poher et al., 2015).”
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“Among the adipose tissues such as vWAT, subcutaneous WAT (sWAT), and brown adipose tissue (BAT) known to be associated with obesity (Cypess and Kahn, 2010; Wajchenberg, 2000), CAG administration (50 mg/kg BW) significantly reduced the weight of visceral fat to 2.47 ± 0.26 g from 2.84 ± 0.31 g in…”
InfluentialScientific literature mining for drug discovery: a case study on obesity
Rajpal, D. K., Kumar, V. D., & Agarwal, P. (2010) · Drug Development Research · doi:10.1002/ddr.20416 · Cited by 7
“Recently, there has been an increase in scientific discussion on brown adipose in comparison to white adipose for obesity and diabetes [Cypess and Kahn, 2010].”
BackgroundWickramasinghe, M., & Weaver, J. U. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-48559-3.00010-5 · Cited by 7
Mariwala, J. K., Rai, D., Padigaru, M., Morde, A. A., Maddox, E., Maalouf, S. W., Smith, K. M., & Heuvel, J. P. V. (2021) · Food Science & Nutrition · doi:10.1002/fsn3.2122 · Cited by 7
“Human fat consists of white adipose tissue (WAT), most associated with energy-storing triglycerides, and brown adipose tissue (BAT), with much higher thermogenic capacity (Cypess & Kahn, 2010).”
BackgroundPET/MRI of glucose metabolic rate, lipid content and perfusion in human brown adipose tissue
Lundström, E., Andersson, J., Engström, M., Lubberink, M., Strand, R., Ahlström, H. K., & Kullberg, J. (2021) · Scientific Reports · doi:10.1038/s41598-021-87768-w · Cited by 7
The effect of cold exposure on serum cholesterol is dependent upon ApoE
He, F., Su, W., Wu, R., Li, H., Lou, L., Wu, A., Xie, L., Du, Y., & Wu, S. (2021) · Journal of Thermal Biology · doi:10.1016/j.jtherbio.2021.102972 · Cited by 6
Chen, H., Wang, H.-C., Sung, C.-C., Hsu, Y.-T., & Sheen, Y. (2025) · Journal of Biomedical Optics · doi:10.1117/1.jbo.30.2.023518 · Cited by 6
“1 Other studies have suggested that changes in the concentration and spatial distribution of these components are markers of many diseases, including cardiovascular diseases, 2 diabetes, 3,4 and cancer.”
Plin5: A potential therapeutic target for type 2 diabetes mellitus
Wei, M., Wang, Y., Zhang, Y.-F., & Qiao, Y. (2025) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-025-01680-1 · Cited by 5
“The recent discovery of adult brown adipose tissue has sparked investigation into its possible use in the management of obesity or T2DM [76, 77].”
SIRT1: A novel guardian of brown fat against metabolic damage
Boutant, M., & Cantó, C. (2016) · Obesity · doi:10.1002/oby.21432 · Cited by 6
Thyroid Hormone Induces Ca2+-Mediated Mitochondrial Activation in Brown Adipocytes
Nguyen, M.-H. T., Ly, D. D., Nguyen, N. T., Qi, X., Yi, H., Shong, M., Cha, S., Park, S., & Park, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168640 · Cited by 6
“Energy dissipation via UCP1 of BAT potentially enhances the total energy expenditure of the whole body up to 20% [4]; therefore, UCP1 activation is considered a potentially promising therapeutic approach for obesity and diabetes treatment [5].”
BackgroundGene Profile of Adipose Tissue of Patients with Pheochromocytoma/Paraganglioma
Klímová, J., Mráz, M., Kratochvílová, H., Lacinová, Z., Novák, K., Michalský, D., Kvasnička, J., Holaj, R., Haluzíková, D., Doležalová, R., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10030586 · Cited by 6
“Connection between BAT and adiposity was already described by many studies in rodents and humans [34].”
BackgroundNegron, S. G., Xu, B., & Lin, Z. (2021) · Journal of Visualized Experiments · doi:10.3791/62332 · Cited by 6
Pirt deficiency has subtle female-specific effects on energy and glucose metabolism in mice
Jall, S., Finan, B., Colldén, G., Fischer, K., Dong, X., Tschöp, M. H., Müller, T. D., & Clemmensen, C. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.02.011 · Cited by 5
Discovery of melanin‐concentrating hormone receptor 1 in brown adipose tissue
Philippe, C., Klebermass, E., Balber, T., Kulterer, O. C., Zeilinger, M., Egger, G., Dumanic, M., Herz, C. T., Kiefer, F. W., Scheuba, C., et al. (2021) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14563 · Cited by 5
Nikolic, M. R., Novakovic, J. N., Ramenskaya, G. V., Kokorekin, V. A., Jeremic, N. S., & Jakovljevic, V. L. (2022) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-022-00944-4 · Cited by 5
“It is considered that imbalance between decreased physical activity, high energy carrying foods and inappropriate central appetite suppression are related to development of obesity [4].”
BackgroundLi, T., Tian, J., Wu, M. C., Tian, Y., & Li, Z. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1330565 · Cited by 6
Ablation of DJ-1 impairs brown fat function in diet-induced obese mice
Silvester, A. J., Aseer, K. R., & Yun, J. W. (2018) · Biochimie · doi:10.1016/j.biochi.2018.08.005 · Cited by 5
Differential Strain-dependent Ovarian and Metabolic Responses in a Mouse Model of PCOS
Binder, A. K., Peecher, D. L., Qvigstad, A. J., Gutierrez, S. D., Magana, J., Banks, D. B., & Korach, K. S. (2023) · Endocrinology · doi:10.1210/endocr/bqad024 · Cited by 5
Imaging Brown Adipose Tissue Using Magnetic Resonance: A Promising Future?
Barker, P. B. (2021) · Radiology · doi:10.1148/radiol.2021210185 · Cited by 5
Qi, M., Janssen, İ., Barinas‐Mitchell, E., Budoff, M. J., Brooks, M. M., Karlamangla, A. S., Derby, C. A., Chang, C. H., Shields, K. J., & Khoudary, S. R. E. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13133 · Cited by 5
Latorre‐Muro, P., Vitale, T., Ravichandran, M., Zhang, K., Palozzi, J. M., Bennett, C. F., Lamas‐Paz, A., Sohn, J. H., Jackson, T. D., Jedrychowski, M. P., et al. (2025) · Nature Cell Biology · doi:10.1038/s41556-024-01555-z · Cited by 5
“However, the molecular mechanisms of interorganelle communication (in particular the components that signal to and regulate the OMM) that sustain cellular energy metabolism during HFD stress in obesity and T2D are largely unknown.”
InfluentialMitochondrial Actions for Fat Browning and Energy Expenditure in White Adipose Tissue
de Andrade, P. B. M., Lopes, A. B., & Alonso‐Vale, M. I. C. (2016) · Journal of Obesity and Overweight · doi:10.15744/2455-7633.2.201 · Cited by 4
Recent advances in brown adipose tissue biology
Shen, Y., Liu, X., Dong, M., Lin, J., Zhao, Q., Lee, H.-J., & Jin, W. (2014) · Chinese Science Bulletin · doi:10.1007/s11434-014-0386-3 · Cited by 4
Gangwar, K., Sabzevari, F. M., & Rambabu, K. (2025) · IEEE Transactions on Medical Imaging · doi:10.1109/tmi.2025.3578283 · Cited by 3
“Recent studies show that in North America, many babies are born fat, and doctors are concerned about the problem [4], [5], [6].”
Liang, L., Chen, J., Zhu, J., Kang, Z., Sun, B., & Zhang, Y. (2025) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5c05665 · Cited by 3
Overweight and obesity in metabolic syndrome
Nedogoda, S. V., & Васильевна, Ц. О. (2025) · Russian Journal of Cardiology · doi:10.15829/1560-4071-2025-6535 · Cited by 4
Molecular and histological evidence of brown adipose tissue in adult cats
Clark, M., Ferguson, D. C., Bunick, D., & Hoenig, M. E. (2012) · The Veterinary Journal · doi:10.1016/j.tvjl.2012.05.029 · Cited by 3
Linking Obesity, Metabolism, and Cancer
Vučenik, I., Jones, L. P., & McLenithan, J. C. (2016) · Springer eBooks · doi:10.1007/978-3-319-11251-0_50 · Cited by 3
Bandesh, K., Traurig, M. T., Chen, P., Hsueh, W., Hanson, R. L., Piaggi, P., & Baier, L. J. (2023) · International Journal of Obesity · doi:10.1038/s41366-023-01278-5 · Cited by 4
Therapeutic of a white adipose tissue-specific bivalent aptamer in obesity
Zhang, Y., Pu, Y. D., Deng, Y., Liu, B., Chen, K., Xu, Y., Tan, W., Liu, H., & Wang, J. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116452 · Cited by 3
Energetics of child’s organism: Qualitative and quantitative specifics
Сонькин, В. Д. (2014) · Human Physiology · doi:10.1134/s0362119714050168 · Cited by 3
Recent advances in human brown fat physiology.
Dv, M., & Muralidhara, K. D. (2011) · PubMed · Cited by 3
Linking Obesity, Metabolism and Cancer
Vučenik, I., Jones, L. P., & McLenithan, J. C. (2015) · Springer eBooks · doi:10.1007/978-3-319-12125-3_50-1 · Cited by 3
Ursolic Acid and Maslinic Acid
Bashir, R. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813922-6.00061-8 · Cited by 3
Bioreactors and microphysiological systems for adipose-based pharmacologic screening
Griffin, M. D., & Abbott, R. D. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819376-1.00011-1 · Cited by 3
Jalloul, W., Moscalu, M., Grierosu, I. C., Ionescu, T. M., Stolniceanu, C. R., Guţu, M. M., Ghizdovăţ, V., Mocanu, V., Azoicăi, D., Iliescu, R., et al. (2022) · Diagnostics · doi:10.3390/diagnostics12123182 · Cited by 3
“Obesity and insulin resistance could be a direct result of an excess of this type of energy supply [35].”
BackgroundSood, P., Kaur, G., Thapa, K., Sharma, K., & Sindhu, R. K. (2024) · Antioxidants · doi:10.1002/9781394270576.ch13 · Cited by 3
El‐Merahbi, R., Karagiannakou, V., Kardinal, R., Seep, L., Lindner, R., Jaeckstein, M. Y., Hildebrand, S., Hasić, M., Korkmaz, E., Jha, A. K., et al. (2026) · Molecular Metabolism · doi:10.1016/j.molmet.2026.102346 · Cited by 2
Role of Adipose Stem Cells Therapy in Obesity
Illouz, Y.-G., Sterodimas, A., & Green, A. C. (2011) · Springer eBooks · doi:10.1007/978-3-642-20012-0_13 · Cited by 2
Brown Adipose Tissue: A New Target for Antiobesity Therapy
Meiliana, A., & Wijaya, A. (2010) · The Indonesian Biomedical Journal · doi:10.18585/inabj.v2i2.115 · Cited by 2
Metadata
- Authors
- Cypess, A. M., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Corresponding author
- Kahn, C Ronald
- Venue
- Current Opinion in Endocrinology, Diabetes & Obesity
- Published
- 2010-04
- Volume
- 17
- Issue
- 2
- Pages
- 143-149
- ISSN
- 1752-296X (ISSN-L)
- PMC
- PMC3593105
- OpenAlex
- W2061096962
- Cited by
- 376
- References
- 75
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 11 · 2023: 28 · 2022: 25 · 2021: 36 · 2020: 34 · 2019: 37 · 2018: 28 · 2017: 29 · 2016: 18 · 2015: 17 · 2014: 21 · 2013: 15 · 2012: 27
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Endocrinology Diabetes and Obesity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (RC1DK087317, DK-082659, K23DK081604, P30DK046200, DK046200, DK087317, DK081604, P30DK036836, R01DK082659)
- National Center for Research Resources (KL2RR025757, RR025757)
- 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, type 2 diabetes, thermogenesis, energy expenditure, weight loss, bat origin
- MeSH terms
- Animals, Adipose Tissue, Brown, Diabetes Mellitus, Humans, Models, Biological, Obesity, Anti-Obesity Agents, Thermogenesis, Body Fat Distribution, Cell Transdifferentiation, Cell- and Tissue-Based Therapy
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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.
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