The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Identification and Importance of Brown Adipose Tissue in Adult Humans
Open accessAbstract
BACKGROUND: Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. METHODS: We analyzed 3640 consecutive (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of (18)F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery. RESULTS: Substantial depots of brown adipose tissue were identified by PET-CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher (18)F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P=0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P=0.007). CONCLUSIONS: Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.
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In the citing paper
“Contrastingly, larger species, like rabbits, sheep, cows, and humans are born with BAT stores, but most of these are gradually replaced by WAT after birth [13, 45, 46].”
From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [13]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Cypess et al. found that not only were women twice as likely as men to have brown adipose tissue signal, they also had a greater mass of brown adipose tissue with higher metabolic activity [12].”
From Sex differences in metabolic homeostasis, diabetes, and obesity (2015) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“This thermogenic effect is mediated by the expression of decoupling protein-1 (UCP1; Cypess et al., 2009).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Cypess et al., 2009
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In the citing paper
“Humans are quite different from rats, with much greater body mass (~200X), only moderately greater BAT mass (~10X), and much lower basal metabolic rate (~0.15X) 13,37,36.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [13]
Experimental — accuracy not yet measuredIn the citing paper
“recent reports revealing significant amounts of metabolically active BAT in adults (146, 147)”
From Altered mitochondrial function in insulin-deficient and insulin-resistant states (2018) · cites this paper as [147]
In the citing paper
“adult humans maintain active depots of BAT [54, 55]”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [54]
In the citing paper
“All the groups showed major depots of metabolically active fat in the cervical–supraclavicular region, a slightly different site from that in rodents and children, where BAT is found mainly situated in the interscapular area.”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [30]
In the citing paper
“However, the real breakthrough arrived in 2009 when five independent groups used PET-CT to identify the presence and study the relevance of BAT in adult humans ([30](#B30), [143](#B143), [165](#B165), [168](#B168), [181](#B181)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [30]
In the citing paper
“The expression of UCP1, DIO2, and the β3-adrenergic receptor was also reported, thereby indicating the potential responsiveness of human BAT to both hormonal and pharmacological stimuli.”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [30]
In the citing paper
“Interestingly, human studies showed that BAT is reduced in obese and diabetic patients, thus indicating that this tissue participates in both cold-induced and diet-induced thermogenesis ([30](#B30)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [30]
In the citing paper
“Second, recent studies have shown that adult humans maintain potentially active brown adipose tissue, making this high energetic tissue a real therapeutic target 13–17.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [13]
In the citing paper
“However, it was only during the past year PET/CT imaging was used to prove conclusively that adult humans possess physiologically active UCP1-positive BAT,13–17.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [13]
In the citing paper
“More importantly, BAT activity correlates inversely with BMI13,14 and percentage body fat 13,14, suggesting a role in energy balance.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [13]
In the citing paper
“Retrospective case series using 18F-FDG PET/CT report this to be less than 10% 13,83.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [13]
In the citing paper
“PET/CT positivity shows seasonal variation 13,16,88, indicating a role of BAT in normal adaptation to cold.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [13]
In the citing paper
“Functional BAT also decreases with age, and is rarely observed in non-stimulated [i.e. no investigator-controlled stimulation such as cold or pharmacological interventions], overweight adults over 64 years-old 13, suggesting a possible role of decreased BAT activity in the development of age-related obesity.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [13]
In the citing paper
“Although it has only recently been proven that adult human BAT is functional and may be involved in protecting against weight loss 13–17, attempts to exploit BAT energy expenditure for treating obesity have been around for decades.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [13]
In the citing paper
“This now needs to be reconsidered since very recent findings indicate that humans do express BAT in the neck region (78, 278, 318, 323) and the amount of BAT correlates inversely with body-mass index (78).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [78]
In the citing paper
“This now needs to be reconsidered since very recent findings indicate that humans do express BAT in the neck region (78, 278, 318, 323) and the amount of BAT correlates inversely with body-mass index (78).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [78]
In the citing paper
“Such depots appear to be less active as a function of aging and/or obesity (151, 164 -167).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [151]
In the citing paper
“The role of adipose tissue mitochondria is most apparent in brown adipose tissue, where flux through the ETC generates heat in the process of thermogenesis, a potentially important mechanism regulating systemic metabolism even in adult humans (149 -152).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [151]
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Citations
Cites
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Cited by
Sorted by citations
Adipose Tissue as an Endocrine Organ
Kershaw, E. E., & Flier, J. S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0395 · Cited by 5,522
European Guidelines for Obesity Management in Adults
Yumuk, V., Tsigos, C., Fried, M., Schindler, K., Busetto, L., Micic, D., & Toplak, H. (2015) · Obesity Facts · doi:10.1159/000442721 · Cited by 3,432
Thyroid Hormone Regulation of Metabolism
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Brown and beige fat: Development, function and therapeutic potential
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Metadata
- Authors
- Cypess, A. M., Lehman, S., Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y.-H., Doria, A., Kolodny, G. M., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Beth Israel Deaconess Medical Center (US)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2009-04-09
- Volume
- 360
- Issue
- 15
- Pages
- 1509-1517
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC2859951
- OpenAlex
- W1965079305
- Cited by
- 4,399
- References
- 41
- Citations by year
- 2026: 146 · 2025: 194 · 2024: 214 · 2023: 224 · 2022: 264 · 2021: 305 · 2020: 331 · 2019: 307 · 2018: 295 · 2017: 313 · 2016: 315 · 2015: 309 · 2014: 250 · 2013: 284 · 2012: 223
- FWCI
- 139.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK055545, DK 33201, DK070722, R21DK070722, P30DK046200, R01DK056690, DK046200-16, R01DK033201, DK55545, T32DK007260, P30DK040561)
- National Center for Research Resources (UL1RR025758, KL2RR025757)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- brown adipose tissue, adults, thermogenesis, UCP1, body mass index, obesity, sex differences, age-related decline, beta-blocker use, outdoor temperature, energy expenditure, non-invasive measurement, immunostaining
- MeSH terms
- Adrenergic beta-Antagonists, Adult, Age Factors, Aged, Blood Glucose, Adipose Tissue, Brown, Energy Metabolism, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neck, Sex Characteristics, Temperature, Body Mass Index, Multivariate Analysis, Logistic Models, Statistics, Nonparametric, Radiopharmaceuticals, Fluorodeoxyglucose F18, Positron-Emission Tomography, Adiposity, Adipocytes, Brown, Young Adult
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