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Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents.

ABSTRACT: 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 T2* from water-fat MRI. FF and T2* 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 T2* correlated positively with adiposity before and after adjustment for sex and age. sBAT FF, but not T2* , 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 T2* might be due to FF being a superior biomarker for BAT and/or to methodological limitations in the T2* quantification.

SUBMITTER: Lundstrom E

PROVIDER: S-EPMC6771901 | biostudies-other | 2019 Sep

REPOSITORIES: biostudies-other

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Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents.

Lundström Elin E Ljungberg Joy J Andersson Jonathan J Manell Hannes H Strand Robin R Forslund Anders A Bergsten Peter P Weghuber Daniel D Mörwald Katharina K Zsoldos Fanni F Widhalm Kurt K Meissnitzer Matthias M Ahlström Håkan H Kullberg Joel J

Pediatric obesity 20190709 9

<h4>Background</h4>Despite therapeutic potential against obesity and diabetes, the associations of brown adipose tissue (BAT) with glucose metabolism in young humans are relatively unexplored.<h4>Objectives</h4>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.<h4>Methods</h4>In 143 subjects (10-20 years), MRI estimates of BAT ...[more]

PMID: 31290284

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Project description:Aim: Magnetic resonance imaging (MRI) is increasingly being used to evaluate brown adipose tissue (BAT) function. Reports on the extent and direction of cold-induced changes in MRI fat fraction and estimated BAT volume vary between studies. Here, we aimed to explore the effect of different fat fraction threshold ranges on outcomes measured by MRI. Moreover, we aimed to investigate the effect of cold exposure on estimated BAT mass and energy content. Methods: The effects of cold exposure at different fat fraction thresholding levels were analyzed in the supraclavicular adipose depot of nine adult males. MRI data were reconstructed, co-registered and analyzed in two ways. First, we analyzed cold-induced changes in fat fraction, T2* relaxation time, volume, mass, and energy of the entire supraclavicular adipose depot at different fat fraction threshold levels. As a control, we assessed fat fraction differences of deltoid subcutaneous adipose tissue (SAT). Second, a local analysis was performed to study changes in fat fraction and T2* on a voxel-level. Thermoneutral and post-cooling data were compared using paired-sample t-tests (p < 0.05). Results: Global analysis unveiled that the largest cold-induced change in fat fraction occurred within a thermoneutral fat fraction range of 30-100% (-3.5 ± 1.9%), without changing the estimated BAT volume. However, the largest cold-induced changes in estimated BAT volume were observed when applying a thermoneutral fat fraction range of 70-100% (-3.8 ± 2.6%). No changes were observed for the deltoid SAT fat fractions. Tissue energy content was reduced from 126 ± 33 to 121 ± 30 kcal, when using a 30-100% fat fraction range, and also depended on different fat fraction thresholds. Voxel-wise analysis showed that while cold exposure changed the fat fraction across nearly all thermoneutral fat fractions, decreases were most pronounced at high thermoneutral fat fractions. Conclusion: Cold-induced changes in fat fraction occurred over the entire range of thermoneutral fat fractions, and were especially found in lipid-rich regions of the supraclavicular adipose depot. Due to the variability in response between lipid-rich and lipid-poor regions, care should be taken when applying fat fraction thresholds for MRI BAT analysis.

Project description:Background & aimsPathologists quantify liver steatosis as the fraction of lipid droplet-containing hepatocytes out of all hepatocytes, whereas the magnetic resonance-determined proton density fat fraction (PDFF) reflects the tissue triacylglycerol concentration. We investigated the linearity, agreement, and correspondence thresholds between histological steatosis and PDFF across the full clinical spectrum of liver fat content associated with non-alcoholic fatty liver disease.MethodsUsing individual patient-level measurements, we conducted a systematic review and meta-analysis of studies comparing histological steatosis with PDFF determined by magnetic resonance spectroscopy or imaging in adults with suspected non-alcoholic fatty liver disease. Linearity was assessed by meta-analysis of correlation coefficients and by linear mixed modelling of pooled data, agreement by Bland-Altman analysis, and thresholds by receiver operating characteristic analysis. To explain observed differences between the methods, we used RNA-seq to determine the fraction of hepatocytes in human liver biopsies.ResultsEligible studies numbered 9 (N = 597). The relationship between PDFF and histology was predominantly linear (r = 0.85 [95% CI, 0.80-0.89]), and their values approximately coincided at 5% steatosis. Above 5% and towards higher levels of steatosis, absolute values of the methods diverged markedly, with histology exceeding PDFF by up to 3.4-fold. On average, 100% histological steatosis corresponded to a PDFF of 33.0% (29.5-36.7%). Targeting at a specificity of 90%, optimal PDFF thresholds to predict histological steatosis grades were ≥5.75% for ≥S1, ≥15.50% for ≥S2, and ≥21.35% for S3. Hepatocytes comprised 58 ± 5% of liver cells, which may partly explain the lower values of PDFF vs. histology.ConclusionsHistological steatosis and PDFF have non-perfect linearity and fundamentally different scales of measurement. Liver fat values obtained using these methods may be rendered comparable by conversion equations or threshold values.Impact and implicationsMagnetic resonance-proton density fat fraction (PDFF) is increasingly being used to measure liver fat in place of the invasive liver biopsy. Understanding the relationship between PDFF and histological steatosis fraction is important for preventing misjudgement of clinical status or treatment effects in patient care. Our analysis revealed that histological steatosis fraction is often significantly higher than PDFF, and their association varies across the spectrum of fatty liver severity. These findings are particularly important for physicians and clinical researchers, who may use these data to interpret PDFF measurements in the context of histologically evaluated liver fat content.

Dataset Information

Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents.

Publications

Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents.

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