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Brown adipose tissue is associated with cardiometabolic health

Abstract

White fat stores excess energy, whereas brown and beige fat are thermogenic and dissipate energy as heat. Thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, although the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is unclear1,2. Here we retrospectively categorized 134,529 18F-fluorodeoxyglucose positron emission tomography–computed tomography scans from 52,487 patients, by presence or absence of BAT, and used propensity score matching to assemble a study cohort. Scans in the study population were initially conducted for indications related to cancer diagnosis, treatment or surveillance, without previous stimulation. We report that individuals with BAT had lower prevalences of cardiometabolic diseases, and the presence of BAT was independently correlated with lower odds of type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure and hypertension. These findings were supported by improved blood glucose, triglyceride and high-density lipoprotein values. The beneficial effects of BAT were more pronounced in individuals with overweight or obesity, indicating that BAT might play a role in mitigating the deleterious effects of obesity. Taken together, our findings highlight a potential role for BAT in promoting cardiometabolic health.

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Fig. 1: Study design, association of brown fat with patient demographics and characterization of brown fat activity across adipose depots.
Fig. 2: Propensity score matching and association of brown fat with medication, cancer site and cancer treatment.
Fig. 3: Association of brown fat with cardiometabolic disease and laboratory values.

Data availability

Average monthly temperatures in Central Park were obtained from the National Weather Service at https://www.weather.gov/media/okx/Climate/CentralPark/monthlyannualtemp.pdf. Anonymized clinical data are available upon request, subject to an internal review by T.B., P.C., A.G.W. and H.S. to ensure that the participants’ anonymity and confidentiality are protected and completion of a data sharing agreement, and in accordance with The Rockefeller University and Memorial Sloan Kettering Cancer Center Institutional Review Board and Institutional Guidelines. Source data are provided with this paper.

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Acknowledgements

We thank M.N. Singer and C. Poon for expert IT support and data extraction; R. Teng for assistance in accessing data; and B.S. Coller, A.J. Dannenberg, J.J. Moslehi and M.D. Curtis for valuable discussions during the preparation of this manuscript. T.B. was supported in part by the National Center for Advancing Translational Sciences, NIH, through The Rockefeller University (grant UL1TR001866). P.C. was supported by the Sinsheimer Foundation and by the American Diabetes Association Pathway Program Accelerator Award (grant 1-17-ACE-17).

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Authors

Contributions

P.C. and T.B. designed and conceived the study. T.B., S.J.M., A.G.W., S.D.B. and H.S. acquired data. P.C., T.B., S.P., M.E., A.G.W., R.V., H.S., C.S.J. and A.M. analyzed and interpreted the data. T.B, D.J.K., M.E. and P.C. wrote the manuscript with input from all authors.

Corresponding author

Correspondence to Paul Cohen.

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The authors declare no competing interests.

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Peer review information Jennifer Sargent was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 Number of 18F-FDG PET/CT scans and brown fat prevalence between 06/2009 - 03/2018.

a, The total number of 18F-FDG PET/CT scans performed at MSKCC between 2009 and 2018 and prevalence of reported brown fat. Dots depict total number of 18F-FDG PET/CT scan in each year, half filled dots illustrate years in which only part of the year was analyzed. Bars represent prevalence of 18F-FDG PET/CT scans with reported brown fat.

Source data

Extended Data Fig. 2 Correlation between brown fat prevalence and body mass index and outside temperature.

a, Correlation between body mass index and prevalence of brown fat reported on 18F-FDG PET/CT. b, Correlation between outside temperature in the month of the scan and prevalence of brown fat reported on 18F-FDG PET/CT.

Source data

Extended Data Fig. 3 Index scan position and cancer treatment.

a, Percentage of patients with BAT (BAT+) and without BAT (BAT-) receiving cancer therapy within 90 days of the index scan. Number in parenthesis indicates position of index scan. b, Percentage of patients with BAT (BAT+) and without 18F-FDG uptake on PET in regions corresponding to fat on CT (BAT-) and the position of the index scan depicted in parenthesis.

Source data

Extended Data Fig. 4 Standardized mean differences before and after propensity score matching.

Propensity score matching was assessed by comparing standardized mean differences before and after the matching process. The blue shaded area indicates standardized mean differences between 0.1 and −0.1.

Extended Data Fig. 5 Assocation of brown fat and cardiometabolic disease and additional adjustment for type II diabetes or index scan position.

a, Forest plots illustrate the association between brown fat status and cardiometabolic disease in the propensity score matched cohort, with additional adjustment for T2DM. Circles and bars represent odds ratios (ORs) and 95% confidence intervals (CIs) respectively. b, Forest plots illustrate the association between brown fat status and cardiometabolic disease in the propensity score matched cohort, with additional adjustment for index scan position. Circles and bars represent odds ratios (ORs) and 95% confidence intervals (CIs), respectively.

Extended Data Fig. 6 Association of brown fat and cardiometabolic disease in the entire cohort.

a, Association between brown fat and cardiometabolic disease in the entire study cohort. b, Forest plots illustrate the association between brown fat status and cardiometabolic disease in the entire study cohort. Circles and bars represent odds ratios (ORs) and 95% confidence intervals (CIs), respectively.

Extended Data Fig. 7 Examples of 18F-FDG uptake on PET in regions corresponding to adipose tissue on CT in patients with cancers of the head and neck.

a, 52-year old, female patient with keratinizing squamous cell carcinoma of the gums (green arrow). 18F-FDG PET/CT indicated for cancer staging. Symmetrical, bilateral 18F-FDG uptake on PET in cervical regions corresponding to adipose tissue on CT (blue arrow). b, 34-year old, female patient with marginal zone B-cell lymphoma of the mouth floor, initial staging scan (green arrow). 18F-FDG PET/CT indicated for cancer staging. Symmetrical, bilateral 18F-FDG uptake on PET in cervical regions corresponding to adipose tissue on CT (blue arrow).

Supplementary information

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Source Data Extended Data Fig. 1

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Becher, T., Palanisamy, S., Kramer, D.J. et al. Brown adipose tissue is associated with cardiometabolic health. Nat Med 27, 58–65 (2021). https://doi.org/10.1038/s41591-020-1126-7

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