Cited by 376Adipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic DiseasesCardiovascular Disease and Adiposity

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Brown fat as a therapy for obesity and diabetes

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Cypess, Aaron M, Kahn, C Ronald·2010·Current Opinion in Endocrinology, Diabetes & Obesity

DOI 10.1097/med.0b013e328337a81fPMC PMC3593105

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Abstract

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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“COPYRIGHT ª 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc. 1896 THE JOURNAL OF NUCLEAR MEDICINE • Vol. 54 • No. 11 • November 2013 BAT activity in both humans and rodent models is routinely achieved through cold exposure (6,8,21), which acts centrally to stimulate the sympathetic nervous system to…”
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Background
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Distinct expression profiles of LncRNAs between brown adipose tissue and skeletal muscle
Zhang, J., Cui, X., Shen, Y., Pang, L., Zhang, A., Fu, Z., Chen, J., Guo, X., Gan, W., & Ji, C. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.12.092 · Cited by 28
“Brown adipose tissue (BAT) which is specialized for thermogenic energy expenditure has attracted people’s focus as a potential target for the treatment of obesity [1].”
Background
Capsinoids suppress diet-induced obesity through uncoupling protein 1-dependent mechanism in mice
Okamatsu‐Ogura, Y., Tsubota, A., Ohyama, K., Nogusa, Y., Saito, M., & Kimura, K. (2015) · Journal of Functional Foods · doi:10.1016/j.jff.2015.09.005 · Cited by 27
Activation of Human Brown Adipose Tissue by Capsinoids, Catechins, Ephedrine, and Other Dietary Components: A Systematic Review
Osuna‐Prieto, F. J., Martínez‐Téllez, B., Sánchez‐Delgado, G., Aguilera, C. M., Lozano‐Sánchez, J., Arraéz-Román, D., Segura‐Carretero, A., & Ruiz, J. R. (2018) · Advances in Nutrition · doi:10.1093/advances/nmy067 · Cited by 26
Brown Adipose Tissue Can Be Activated or Inhibited within an Hour before 18F‐FDG Injection: A Preliminary Study with MicroPET
Wu, C., Cheng, W., Xing, H., Dang, Y., Li, F., & Zhu, Z. (2011) · BioMed Research International · doi:10.1155/2011/159834 · Cited by 26
“These functional BATs have drawn our attention as a potential therapeutic target for inducing weight loss through its energy expenditure pathway [2, 5], because excision or denervation of interscapular BAT can produce abnormal increase in the amounts of WAT in those animals, meaning that they are becoming fatter [6].”
Background
Amplification of Adipogenic Commitment by VSTM2A
Secco, B., Camiré, É., Brière, M.-A., Caron, A., Billong, A., Gélinas, Y., Lemay, A., Tharp, K. M., Lee, P. L., Gobeil, S., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.015 · Cited by 32
“Owing to its significant capacity to dissipate energy and regulate metabolism, this tissue is envisioned as a potential target for the treatment of obesity and diabetes (Cypess and Kahn, 2010).”
Background
Role of BMP7 in appetite regulation, adipogenesis, and energy expenditure
Saini, S., Duraisamy, A. J., Bayen, S., Vats, P., & Singh, S. B. (2014) · Endocrine · doi:10.1007/s12020-014-0406-8 · Cited by 28
“Highly vascularized BAT is derived from differentiation of mesenchymal stem cell [9, 44, 45] and has a large number of mitochondria for carrying out b-oxidation [17].”
BackgroundInfluential
Low glycemic load diets protect against metabolic syndrome and Type 2 diabetes mellitus in the male Nile rat
Bolsinger, J., Landstrom, M., Prończuk, A., Auerbach, A. D., & Hayes, K. C. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.01.007 · Cited by 26
Developmental exposure to DDT or DDE alters sympathetic innervation of brown adipose in adult female mice
vonderEmbse, A. N., Elmore, S. E., Jackson, K. B., Habecker, B. A., Manz, K. E., Pennell, K. D., Lein, P. J., & Merrill, M. A. L. (2021) · Environmental Health · doi:10.1186/s12940-021-00721-2 · Cited by 26
Epigallocatechin Exerts Anti‐Obesity Effect in Brown Adipose Tissue
Kim, Y., Moon, J., Kim, Y., & Huh, J. Y. (2019) · Chemistry & Biodiversity · doi:10.1002/cbdv.201900347 · Cited by 26
“Therefore, BAT has been suggested as a potential target for anti-obesity therapy.[10] The phenomenon of ‘browning’ in certain WAT has very attractive target for thermogenic and fat-burning properties.”
Background
Potential of Nutraceutical Supplementation in the Modulation of White and Brown Fat Tissues in Obesity-Associated Disorders: Role of Inflammatory Signalling
Scarano, F., Gliozzi, M., Zito, M. C., Guarnieri, L., Carresi, C., Macrì, R., Nucera, S., Scicchitano, M., Bosco, F., Ruga, S., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073351 · Cited by 30
“Unlike WAT, which stores energy, mammals, including humans, have brown adipose tissue (BAT), which is specialized for energy expenditure, a process known as thermogenesis, with a potential role against obesity and associated metabolic diseases [10].”
Background
Activation of Brown Adipose Tissue and Promotion of White Adipose Tissue Browning by Plant-based Dietary Components in Rodents: A Systematic Review
Osuna‐Prieto, F. J., Martínez‐Téllez, B., Segura‐Carretero, A., & Ruiz, J. R. (2021) · Advances in Nutrition · doi:10.1093/advances/nmab084 · Cited by 26
Allosteric regulation of thioesterase superfamily member 1 by lipid sensor domain binding fatty acids and lysophosphatidylcholine
Tillman, M. C., Imai, N., Li, Y., Khadka, M., Okafor, C. D., Juneja, P., Adhiyaman, A., Hagen, S. J., Cohen, D. E., & Ortlund, E. A. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003877117 · Cited by 26
“Because high rates of caloric consumption are required to generate heat, pharmacologic approaches to increasing BAT mass and activity are viewed as promising objectives in the management of obesity and related metabolic disorders (3).”
Background
Reliability and agreement of adipose tissue fat fraction measurements with water–fat MRI in patients with manifest cardiovascular disease
Franssens, B. T., Eikendal, A. L. M., Leiner, T., van der Graaf, Y., Visseren, F. L. J., & Hoogduin, J. M. (2015) · NMR in Biomedicine · doi:10.1002/nbm.3444 · Cited by 25
Benefits of healthy adipose tissue in the treatment of diabetes
Gunawardana, S. C. (2014) · World Journal of Diabetes · doi:10.4239/wjd.v5.i4.420 · Cited by 26
Determination of a pharmacokinetic model for [11C]-acetate in brown adipose tissue
Richard, M. A., Blondin, D. P., Noll, C., Lebel, R., Lepage, M., & Carpentier, A. C. (2019) · EJNMMI Research · doi:10.1186/s13550-019-0497-6 · Cited by 24
“That is one reason why strategies to increase metabolism, such as activation of brown adipose tissue (BAT) thermogenesis, are appealing to counter metabolic disorders [4].”
Background
Adipose transplant for inborn errors of branched chain amino acid metabolism in mice
Zimmerman, H. A., Olson, K. C., Chen, G., & Lynch, C. J. (2013) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2013.05.010 · Cited by 24
Stimulatory, but not anxiogenic, doses of caffeine act centrally to activate interscapular brown adipose tissue thermogenesis in anesthetized male rats
Schaik, L. V., Kettle, C., Green, R. A., Sievers, W., Hale, M. W., Irving, H. R., Whelan, D. R., & Rathner, J. A. (2021) · Scientific Reports · doi:10.1038/s41598-020-80505-9 · Cited by 23
Metabolic Effects of FGF-21: Thermoregulation and Beyond
Ni, B., Farrar, J. S., Vaitkus, J. A., & Celi, F. S. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00148 · Cited by 23
Teneurin-2 (TENM2) deficiency induces UCP1 expression in differentiating human fat cells
Tews, D., Fromme, T., Keuper, M., Hofmann, S. M., Debatin, K., Klingenspor, M., Wabitsch, M., & Fischer‐Posovszky, P. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.01.015 · Cited by 23
Supplementation of Fermented Barley Extracts with Lactobacillus Plantarum dy-1 Inhibits Obesity via a UCP1-dependent Mechanism.
Xiao, X., Bai, J., Li, M. S., Zhang, J. Y., Sun, X., & Dong, Y. (2019) · PubMed · doi:10.3967/bes2019.076 · Cited by 23
Functionally enhanced brown adipose tissue in Ames dwarf mice
Darcy, J., & Bartke, A. (2016) · Adipocyte · doi:10.1080/21623945.2016.1274470 · Cited by 22
“However, with the discovery of BAT in adult humans,(31) increasing BAT activity as a means to increase energy expenditure has become a new target for combating obesity.(32) Most research in this area has focused on pharmacological modulation of BAT”
Background
Mapping Research in the Obesity, Adipose Tissue, and MicroRNA Field: A Bibliometric Analysis
Alves, J. M., Teles, R. H. G., Gatto, C. D. V. G., Muñoz, V. R., Cominetti, M. R., & Duarte, A. C. G. D. O. (2019) · Cells · doi:10.3390/cells8121581 · Cited by 22
Remodeling of gene regulatory networks underlying thermogenic stimuli-induced adipose beiging
Lee, S. Y., Benvie, A. M., Park, H. G., Spektor, R., Harlan, B. A., Brenna, J. T., Berry, D. C., & Soloway, P. D. (2022) · Communications Biology · doi:10.1038/s42003-022-03531-5 · Cited by 23
“Given these results, and the facts that (1) individual cells can move between cell states in the same cell type, and (2) cells may exist in transition between states54, we sought to find a path covering the heterogeneous cellular states in the context of continuous beige adipocyte developmental trajectory.”
Background
Differential remodeling of subcutaneous white and interscapular brown adipose tissue by long-term exercise training in aged obese female mice
Félix‐Soriano, E., Sáinź, N., Gil‐Iturbe, E., Castilla‐Madrigal, R., Celay, J., Fernández‐Galilea, M., Pejenaute, Á., Lostao, M. P., Martinez-Climent, J. A., & Moreno-Aliaga, M. J. (2023) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-023-00964-2 · Cited by 23
“Although BAT represents only 1–2% of body fat [38], BAT is relevant for the regulation of energy homeostasis and the prevention of obesity [14].”
Background
Berardinelli-Seip Congenital Lipodystrophy 2/Seipin Is Not Required for Brown Adipogenesis but Regulates Brown Adipose Tissue Development and Function
Zhou, H., Black, S. M., Benson, T. W., Weintraub, N. L., & Chen, W. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.01120-15 · Cited by 21
“Thus, interventions to increase BAT mass/activity could potentially promote adaptive energy expenditure to combat obesity (9, 10).”
Background
RGS2: A multifunctional signaling hub that balances brown adipose tissue function and differentiation
Klepac, K., Yang, J.-H., Hildebrand, S., & Pfeifer, A. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.015 · Cited by 22
“Almost a decade ago, several laboratories located across different continents reported that adult humans possess active brown adipose tissue (BAT) and that BAT activity is inversely correlated with body mass index in human adults [1e4], a finding that ignited intense research on its therapeutic potential [5,6].”
Background
Halftone spatial frequency domain imaging enables kilohertz high-speed label-free non-contact quantitative mapping of optical properties for strongly turbid media
Zhao, Y., Song, B., Wang, M., Zhao, Y., & Fan, Y. (2021) · Light Science & Applications · doi:10.1038/s41377-021-00681-9 · Cited by 21
Honokiol exerts dual effects on browning and apoptosis of adipocytes
Lone, J. B., & Yun, J. W. (2017) · Pharmacological Reports · doi:10.1016/j.pharep.2017.06.004 · Cited by 21
Mitochondria-associated regulation in adipose tissues and potential reagents for obesity intervention
Zheng, Y., Ni, Y., Pang, Y., Gong, Y., Yang, H., Ding, W., & Yang, H. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1132342 · Cited by 20
“Therefore, targeting mitochondria to activate UCP1 is a strategy to treat obesity (15).”
Background
Biology and pathological implications of brown adipose tissue: promises and caveats for the control of obesity and its associated complications
Tapía, P., Fernández‐Galilea, M., Robledo, F., Mardones, P., Galgani, J. E., & Cortés, V. (2017) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12389 · Cited by 21
Lesser Investigated Natural Ingredients for the Management of Obesity
Majeed, M. A., Majeed, S., Nagabhushanam, K., Muthuraman, G., & Mundkur, L. (2021) · Nutrients · doi:10.3390/nu13020510 · Cited by 20
“The brown and the beige adipocytes contain numerous mitochondria and express the uncoupling protein 1 (UCP-1), which regulates energy expenditure, reduces adiposity, and protects experimental animals from diet-induced obesity [25].”
Background
Chronic alcohol consumption decreases brown adipose tissue mass and disrupts thermoregulation: a possible role for altered retinoid signaling
Blaner, W. S., Gao, M. A., Jiang, H., Dalmer, T. R. A., Hu, X. J., Ginsberg, H. N., & Clugston, R. D. (2017) · Scientific Reports · doi:10.1038/srep43474 · Cited by 20
Cutaneous changes in diabetic patients: Primed for aberrant healing?
Chen, V. Y., Siegfried, L. G., Tomic‐Canic, M., Stone, R. C., & Pastar, I. (2023) · Wound Repair and Regeneration · doi:10.1111/wrr.13108 · Cited by 24
In Vitro and in Vivo Analyses Reveal Profound Effects of Fibroblast Growth Factor 16 as a Metabolic Regulator
Rulifson, I. C., Collins, P. J., Miao, L., Nojima, D., Lee, K. J., Hardy, M., Gupte, J., Hensley, K. M., Samayoa, K., Cam, C., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.751404 · Cited by 19
“Accordingly, in mice, BAT-mediated thermogenesis suppresses high fat diet-induced obesity (3–5), and in humans the presence of active BAT inversely correlates with adiposity (6, 7).”
Background
Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI
Andersson, J., Lundström, E., Engström, M., Lubberink, M., Ahlström, H. K., & Kullberg, J. (2019) · Scientific Reports · doi:10.1038/s41598-019-48879-7 · Cited by 19
Berardinelli–Seip congenital lipodystrophy 2/SEIPIN determines brown adipose tissue maintenance and thermogenic programing
Zhou, H., Xu, C., Lee, H., Yoon, Y., & Chen, W. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.02.014 · Cited by 17
Liraglutide suppresses obesity and promotes browning of white fat via miR-27b in vivo and in vitro
Wang, X., Chen, S., Lv, D., Li, Z., Ren, L., Zhu, H., Xie, X., & Liu, Y. (2021) · Journal of International Medical Research · doi:10.1177/03000605211055059 · Cited by 18
“Generally, weight loss is achieved by mechanisms including reduced adipogenesis and increased thermogenesis.(24) Adipogenesis is a cellular Figure 3.”
Background
Peanut Shell Extract and Luteolin Regulate Lipid Metabolism and Induce Browning in 3T3-L1 Adipocytes
Liu, W., Wang, L., & Zhang, J. (2022) · Foods · doi:10.3390/foods11172696 · Cited by 19
“Browning refers to the transition from WAT to beige adipose [16].”
Background
A general overview of the multifactorial adaptation to cold: biochemical mechanisms and strategies
Ramón, A., Esteves, A., Villadóniga, C., Chalar, C., & Castro‐Sowinski, S. (2023) · Brazilian Journal of Microbiology · doi:10.1007/s42770-023-01057-4 · Cited by 21
The effects of sodium butyrate supplementation on the expression levels of PGC-1α, PPARα, and UCP-1 genes, serum level of GLP-1, metabolic parameters, and anthropometric indices in obese individuals on weight loss diet: a study protocol for a triple-blind, randomized, placebo-controlled clinical trial
Amiri, P., Hosseini, S. A., Roshanravan, N., Saghafi‐Asl, M., & Tootoonchian, M. (2023) · Trials · doi:10.1186/s13063-022-06891-9 · Cited by 18
The Effects of Graded Levels of Calorie Restriction: XIV. Global Metabolomics Screen Reveals Brown Adipose Tissue Changes in Amino Acids, Catecholamines, and Antioxidants After Short-Term Restriction in C57BL/6 Mice
Green, C. L., Mitchell, S. E., Derous, D., Wang, Y., Chen, L., Han, J. J., Promislow, D., Lusseau, D., Douglas, A., & Speakman, J. R. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz023 · Cited by 18
“Because of this process, BAT has become very interesting in terms of aging-associated diseases such as type 2 diabetes and obesity (7,8).”
Background

Authors: Cypess, A. M., & Kahn, C. R.
Affiliations: Joslin Diabetes Center (US)
Corresponding author: Kahn, C Ronald
ORCID: Cypess, Aaron M
Kahn, C Ronald
Venue: Current Opinion in Endocrinology, Diabetes & Obesity
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2010-04
Volume: 17
Issue: 2
Pages: 143-149
ISSN: 1752-296X (ISSN-L)
DOI: 10.1097/med.0b013e328337a81f
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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Brown fat as a therapy for obesity and diabetes

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