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      Decreased insulin‐stimulated brown adipose tissue glucose uptake after short‐term exercise training in healthy middle‐aged men

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          Abstract

          Aims

          To test the hypothesis that high‐intensity interval training (HIIT) and moderate‐intensity continuous training (MICT) improve brown adipose tissue (BAT) insulin sensitivity.

          Participants and methods

          Healthy middle‐aged men (n = 18, age 47 years [95% confidence interval {CI} 49, 43], body mass index 25.3 kg/m 2 [95% CI 24.1‐26.3], peak oxygen uptake (VO 2peak) 34.8 mL/kg/min [95% CI 32.1, 37.4] ) were recruited and randomized into six HIIT or MICT sessions within 2 weeks. Insulin‐stimulated glucose uptake was measured using 2‐[ 18F]flouro‐2‐deoxy‐D‐glucose positron‐emission tomography in BAT, skeletal muscle, and abdominal and femoral subcutaneous and visceral white adipose tissue (WAT) depots before and after the training interventions.

          Results

          Training improved VO 2peak ( P = .0005), insulin‐stimulated glucose uptake into the quadriceps femoris muscle ( P = .0009) and femoral subcutaneous WAT ( P = .02) but not into BAT, with no difference between the training modes. Using pre‐intervention BAT glucose uptake, we next stratified subjects into high BAT (>2.9 µmol/100 g/min; n = 6) or low BAT (<2.9 µmol/100 g/min; n = 12) groups. Interestingly, training decreased insulin‐stimulated BAT glucose uptake in the high BAT group (4.0 [2.8, 5.5] vs 2.5 [1.7, 3.6]; training*BAT, P = .02), whereas there was no effect of training in the low BAT group (1.5 [1.2, 1.9] vs 1.6 [1.2, 2.0] µmol/100 g/min). Participants in the high BAT group had lower levels of inflammatory markers compared with those in the low BAT group.

          Conclusions

          Participants with functionally active BAT have an improved metabolic profile compared with those with low BAT activity. Short‐term exercise training decreased insulin‐stimulated BAT glucose uptake in participants with active BAT, suggesting that training does not work as a potent stimulus for BAT activation.

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          Most cited references36

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          Identification and Importance of Brown Adipose Tissue in Adult Humans

          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. 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. 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). 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. 2009 Massachusetts Medical Society
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            Functional Brown Adipose Tissue in Healthy Adults

            Using positron-emission tomography (PET), we found that cold-induced glucose uptake was increased by a factor of 15 in paracervical and supraclavicular adipose tissue in five healthy subjects. We obtained biopsy specimens of this tissue from the first three consecutive subjects and documented messenger RNA (mRNA) and protein levels of the brown-adipocyte marker, uncoupling protein 1 (UCP1). Together with morphologic assessment, which showed numerous multilocular, intracellular lipid droplets, and with the results of biochemical analysis, these findings document the presence of substantial amounts of metabolically active brown adipose tissue in healthy adult humans. 2009 Massachusetts Medical Society
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              Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans.

              Brown adipose tissue (BAT) is vital for proper thermogenesis during cold exposure in rodents, but until recently its presence in adult humans and its contribution to human metabolism were thought to be minimal or insignificant. Recent studies using PET with 18F-fluorodeoxyglucose (18FDG) have shown the presence of BAT in adult humans. However, whether BAT contributes to cold-induced nonshivering thermogenesis in humans has not been proven. Using PET with 11C-acetate, 18FDG, and 18F-fluoro-thiaheptadecanoic acid (18FTHA), a fatty acid tracer, we have quantified BAT oxidative metabolism and glucose and nonesterified fatty acid (NEFA) turnover in 6 healthy men under controlled cold exposure conditions. All subjects displayed substantial NEFA and glucose uptake upon cold exposure. Furthermore, we demonstrated cold-induced activation of oxidative metabolism in BAT, but not in adjoining skeletal muscles and subcutaneous adipose tissue. This activation was associated with an increase in total energy expenditure. We found an inverse relationship between BAT activity and shivering. We also observed an increase in BAT radio density upon cold exposure, indicating reduced BAT triglyceride content. In sum, our study provides evidence that BAT acts as a nonshivering thermogenesis effector in humans.
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                Author and article information

                Contributors
                jarna.hannukainen@tyks.fi
                Journal
                Diabetes Obes Metab
                Diabetes Obes Metab
                10.1111/(ISSN)1463-1326
                DOM
                Diabetes, Obesity & Metabolism
                Blackwell Publishing Ltd (Oxford, UK )
                1462-8902
                1463-1326
                06 July 2017
                October 2017
                : 19
                : 10 ( doiID: 10.1111/dom.2017.19.issue-10 )
                : 1379-1388
                Affiliations
                [ 1 ] Turku PET Centre University of Turku Turku Finland
                [ 2 ] Section on Integrative Physiology and Metabolism Joslin Diabetes Center, Harvard Medical School Boston Massachusetts
                [ 3 ] Division of Endocrinology, Diabetes and Metabolism Beth Israel Deaconess Medical Center Boston Massachusetts
                [ 4 ] Department of Clinical Physiology and Nuclear Medicine Turku University Hospital Turku Finland
                [ 5 ] Department of Physical Performance Norwegian School of Sport Sciences Oslo Norway
                [ 6 ] Department of Medical Physics Turku University Hospital Turku Finland
                [ 7 ] Department of Radiology Turku University Hospital Turku Finland
                [ 8 ] Department of Biostatistics University of Turku Turku Finland
                [ 9 ] Turku PET Centre Åbo Akademi University Turku Finland
                [ 10 ] Department of Endocrinology Turku University Hospital Turku Finland
                Author notes
                [*] [* ] Correspondence Jarna C. Hannukainen PhD, Turku PET Centre, University of Turku, Turku PO Box 52, FIN‐20521, Finland. Email: jarna.hannukainen@ 123456tyks.fi
                Author information
                http://orcid.org/0000-0002-2876-1851
                Article
                DOM12947
                10.1111/dom.12947
                5607085
                28318098
                e6444b4d-f0a7-4e15-ad33-d2b571ef8a2a
                © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 19 January 2017
                : 03 March 2017
                : 15 March 2017
                Page count
                Figures: 3, Tables: 2, Pages: 10, Words: 7072
                Funding
                Funded by: Academy of Finland
                Award ID: 251399
                Award ID: 256470
                Funded by: University of Turku
                Funded by: Turku University Hospital
                Funded by: Åbo Akademi University
                Funded by: European Foundation for the Study of Diabetes
                Funded by: Emil Aaltonen Foundation
                Funded by: Hospital District of Southwest Finland
                Funded by: Orion Research Foundation
                Funded by: Finnish Diabetes Foundation
                Funded by: Ministry of Education of the State of Finland
                Funded by: EU FP7 project DIABAT
                Award ID: HEALTH‐F2‐2011‐278373
                Funded by: Paavo Nurmi Foundation
                Funded by: Novo Nordisk Foundation
                Funded by: National Institutes of Health
                Award ID: R01‐DK099511
                Award ID: RO1‐DK112283
                Funded by: Joslin Diabetes Center DERC
                Award ID: 5P30DK36836
                Award ID: T32‐DK‐07260‐038
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                dom12947
                dom12947-hdr-0001
                October 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.1 mode:remove_FC converted:12.10.2017

                Endocrinology & Diabetes
                brown adipose tissue,exercise training,glucose uptake,free fatty acid uptake,positron emission tomography

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