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Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.ORCID iD: 0000-0003-2955-4958
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.ORCID iD: 0000-0002-6209-591X
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.ORCID iD: 0000-0001-6477-2331
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.ORCID iD: 0000-0002-5209-4841
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2019 (English)In: Pediatric Obesity, ISSN 2047-6302, E-ISSN 2047-6310, Vol. 14, no 9, article id e12531Article in journal (Refereed) Published
Abstract [en]

Background

Despite therapeutic potential against obesity and diabetes, the associations of brown adipose tissue (BAT) with glucose metabolism in young humans are relatively unexplored.

Objectives

To investigate possible associations between magnetic resonance imaging (MRI) estimates of BAT and glucose metabolism, whilst considering sex, age, and adiposity, in adolescents with normal and overweight/obese phenotypes.

Methods

In 143 subjects (10‐20 years), MRI estimates of BAT were assessed as cervical‐supraclavicular adipose tissue (sBAT) fat fraction (FF) and T*2 from water‐fat MRI. FF and T*2 of neighbouring subcutaneous adipose tissue (SAT) were also assessed. Adiposity was estimated with a standardized body mass index, the waist‐to‐height ratio, and abdominal visceral and subcutaneous adipose tissue volumes. Glucose metabolism was represented by the 2h plasma glucose concentration, the Matsuda index, the homeostatic model assessment of insulin resistance, and the oral disposition index; obtained from oral glucose tolerance tests.

Results

sBAT FF and T*2 correlated positively with adiposity before and after adjustment for sex and age. sBAT FF, but not T*2, correlated with 2h glucose and Matsuda index, also after adjustment for sex, age, and adiposity. The association with 2h glucose persisted after additional adjustment for SAT FF.

Conclusions

The association between sBAT FF and 2h glucose, observed independently of sex, age, adiposity, and SAT FF, indicates a role for BAT in glucose metabolism, which potentially could influence the risk of developing diabetes. The lacking association with sBAT T*2 might be due to FF being a superior biomarker for BAT and/or to methodological limitations in the T*2 quantification.

Place, publisher, year, edition, pages
2019. Vol. 14, no 9, article id e12531
Keywords [en]
adolescent, brown adipose tissue, glucose metabolism, magnetic resonance imaging
National Category
Pediatrics Medical Image Processing
Identifiers
URN: urn:nbn:se:uu:diva-380052DOI: 10.1111/ijpo.12531ISI: 000482155600007PubMedID: 31290284OAI: oai:DiVA.org:uu-380052DiVA, id: diva2:1298405
Funder
Swedish Heart Lung Foundation, 2170492Swedish Research Council, 2016-01040EU, FP7, Seventh Framework Programme, 279153Available from: 2019-07-09 Created: 2019-03-22 Last updated: 2019-10-23Bibliographically approved
In thesis
1. Magnetic Resonance Imaging of Human Brown Adipose Tissue: Methodological Development and Application
Open this publication in new window or tab >>Magnetic Resonance Imaging of Human Brown Adipose Tissue: Methodological Development and Application
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Brown adipose tissue (BAT) is a thermogenic organ with the main human depot located in the cervical-supraclavicular (sBAT) region. BAT is proposed as a potential therapeutic target for obesity and diabetes. This thesis aims to contribute to the development of magnetic resonance imaging (MRI)-based methods and to the application of these in studies of human BAT. Water-fat MRI enables separation of water and fat, the dominant contributors to the MR signal, and the quantification of fat fraction (FF) and effective transverse relaxation rate (R2*). FF and R2* are often used in studies of human BAT, e.g. for characterizing the tissue and distinguishing it from white adipose tissue. A Cooling-reheating protocol was introduced for studying changes in sBAT, related to lipid content and perfusion. sBAT FF decreased after cold exposure. The sustained low FF after reheating suggested lipid consumption as the primary cause. This conclusion was based on the assumption of a normalized perfusion after reheating. An automated method for segmentation of sBAT was developed. The method compared well with a semi-automated reference method with respect to segmentation overlap and estimated mean sBAT FF and R2*. A modified version of the automated method was applied to a large-scale study where an association between sBAT FF and glucose tolerance indicated a role for BAT in glucose metabolism, potentially linked to the risk of developing diabetes.  A Cooling-reheating protocol was evaluated with positron emission tomography measurements of perfusion and cold-stimulated BAT activity. Inverse correlations between sBAT FF and BAT activity suggested sBAT FF to predict cold-induced BAT activity. After reheating, the cold-induced increase in perfusion normalized and the cold-induced decrease in FF partially normalized. This suggested potential decreases in FF after reheating to mainly be due to lipid consumption and decreases in FF after cold exposure to possibly be influenced by perfusion.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 83
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1572
Keywords
Brown adipose tissue, Magnetic resonance imaging, Positron emission tomography, Image segmentation, Glucose metabolism
National Category
Medical and Health Sciences Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-381766 (URN)978-91-513-0651-3 (ISBN)
Public defence
2019-06-07, Rosénsalen, Entrance 95/96, Akademiska sjukhuset, Uppsala, 09:15 (English)
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Supervisors
Available from: 2019-05-17 Created: 2019-04-15 Last updated: 2019-06-18

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Lundström, ElinLjungberg, JoyAndersson, JonathanManell, HannesStrand, RobinForslund, AndersBergsten, PeterAhlström, HåkanKullberg, Joel

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Lundström, ElinLjungberg, JoyAndersson, JonathanManell, HannesStrand, RobinForslund, AndersBergsten, PeterAhlström, HåkanKullberg, Joel
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RadiologyDepartment of Medical Cell BiologyDepartment of Women's and Children's HealthDivision of Visual Information and InteractionComputerized Image Analysis and Human-Computer InteractionPaediatric Inflammation, Metabolism and Child Health Research
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Pediatric Obesity
PediatricsMedical Image Processing

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