Dataset Information

Regulation of human brown adipose tissue by adenosine and A2A receptors - studies with [15O]H2O and [11C]TMSX PET/CT.

ABSTRACT: PURPOSE:Brown adipose tissue (BAT) has emerged as a potential target to combat obesity and diabetes, but novel strategies to activate BAT are needed. Adenosine and A2A receptor (A2AR) agonism activate BAT in rodents, and endogenous adenosine is released locally in BAT as a by-product of noradrenaline, but physiological data from humans is lacking. The purpose of this pilot study was to investigate the effects of exogenous adenosine on human BAT perfusion, and to determine the density of A2ARs in human BAT in vivo for the first time, using PET/CT imaging. METHODS:Healthy, lean men (n?=?10) participated in PET/CT imaging with two radioligands. Perfusion of BAT, white adipose tissue (WAT) and muscle was quantified with [15O]H2O at baseline, during cold exposure and during intravenous administration of adenosine. A2AR density of the tissues was quantified with [11C]TMSX at baseline and during cold exposure. RESULTS:Adenosine increased the perfusion of BAT even more than cold exposure (baseline 8.3?±?4.5, cold 19.6?±?9.3, adenosine 28.6?±?7.9 ml/100 g/min, p?

SUBMITTER: Lahesmaa M

PROVIDER: S-EPMC6351510 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Regulation of human brown adipose tissue by adenosine and A2A receptors - studies with [15O]H2O and [11C]TMSX PET/CT.

Lahesmaa Minna M Oikonen Vesa V Helin Semi S Luoto Pauliina P U Din Mueez M Pfeifer Alexander A Nuutila Pirjo P Virtanen Kirsi A KA

European journal of nuclear medicine and molecular imaging 20180813 3

<h4>Purpose</h4>Brown adipose tissue (BAT) has emerged as a potential target to combat obesity and diabetes, but novel strategies to activate BAT are needed. Adenosine and A2A receptor (A2AR) agonism activate BAT in rodents, and endogenous adenosine is released locally in BAT as a by-product of noradrenaline, but physiological data from humans is lacking. The purpose of this pilot study was to investigate the effects of exogenous adenosine on human BAT perfusion, and to determine the ...[more]

PMID: 30105585

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Project description:BackgroundBrown adipose tissue (BAT) is a thermogenic tissue which can generate heat in response to mild cold exposure. As it constitutes a promising target in the fight against obesity, we need reliable techniques to quantify its activity in response to therapeutic interventions. The current standard for the quantification of BAT activity is [18F]FDG PET/CT. Various sequences in magnetic resonance imaging (MRI), including those measuring its relative fat content (fat fraction), have been proposed and evaluated in small proof-of-principle studies, showing diverging results. Here, we systematically compare the predictive value of adipose tissue fat fraction measured by MRI to the results of [18F]FDG PET/CT.MethodsWe analyzed the diagnostic reliability of MRI measured fat fraction (FF) for the estimation of human BAT activity in two cohorts of healthy volunteers participating in two prospective clinical trials (NCT03189511, NCT03269747). In both cohorts, BAT activity was stimulated by mild cold exposure. In cohort 1, we performed [18F]FDG PET/MRI; in cohort 2, we used [18F]FDG PET/CT followed by MRI. Fat fraction was determined by 2-point Dixon and 6-point Dixon measurement, respectively. Fat fraction values were compared to SUVmean in the corresponding tissue depot by simple linear regression.ResultsIn total, 33 male participants with a mean age of 23.9 years and a mean BMI of 22.8 kg/m2 were recruited. In 32 participants, active BAT was visible. On an intra-individual level, FF was significantly lower in high-SUV areas compared to low-SUV areas (cohort 1: p < 0.0001 and cohort 2: p = 0.0002). The FF of the supraclavicular adipose tissue depot was inversely related to its metabolic activity (SUVmean) in both cohorts (cohort 1: R2 = 0.18, p = 0.09 and cohort 2: R2 = 0.42, p = 0.009).ConclusionMRI FF explains only about 40% of the variation in BAT glucose uptake. Thus, it can currently not be used to substitute [18F] FDG PET-based imaging for quantification of BAT activity.Trial registrationClinicalTrials.gov. NCT03189511 , registered on June 17, 2017, actual study start date was on May 31, 2017, retrospectively registered. NCT03269747 , registered on September 01, 2017.

Dataset Information

Regulation of human brown adipose tissue by adenosine and A2A receptors - studies with [15O]H2O and [11C]TMSX PET/CT.

Publications

Regulation of human brown adipose tissue by adenosine and A<sub>2A</sub> receptors - studies with [<sup>15</sup>O]H<sub>2</sub>O and [<sup>11</sup>C]TMSX PET/CT.

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