Exosomal microRNA miR-92a concentration in serum reflects human brown fat activity

Brown adipose tissue (BAT) dissipates energy and its activity correlates with leanness in human adults. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography coupled with computer tomography (PET/CT) is still the standard for measuring BAT activity, but exposes subjects to ionizing radiat...

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Published in	Nature communications Vol. 7; no. 1; pp. 11420 - 9
Main Authors	Chen, Yong, Buyel, Joschka J., Hanssen, Mark J. W., Siegel, Franziska, Pan, Ruping, Naumann, Jennifer, Schell, Michael, van der Lans, Anouk, Schlein, Christian, Froehlich, Holger, Heeren, Joerg, Virtanen, Kirsi A., van Marken Lichtenbelt, Wouter, Pfeifer, Alexander
Format	Journal Article
Language	English
Published	London Nature Publishing Group UK 27.04.2016 Nature Publishing Group Nature Portfolio
Subjects	13 13/106 13/109 13/44 38 38/90 631/337/384/331 631/443 692/308 692/53 Adipose tissue Adipose Tissue, Brown - metabolism Adult Animals Biomarkers Body fat Cohort Studies Exosomes - metabolism Female Humanities and Social Sciences Humans Ionizing radiation Kinases Male Mice, Inbred C57BL MicroRNAs MicroRNAs - blood multidisciplinary Science Science (multidisciplinary) Young Adult Germany Finland
Online Access	Get full text
ISSN	2041-1723 2041-1723
DOI	10.1038/ncomms11420

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Abstract	Brown adipose tissue (BAT) dissipates energy and its activity correlates with leanness in human adults. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography coupled with computer tomography (PET/CT) is still the standard for measuring BAT activity, but exposes subjects to ionizing radiation. To study BAT function in large human cohorts, novel diagnostic tools are needed. Here we show that brown adipocytes release exosomes and that BAT activation increases exosome release. Profiling miRNAs in exosomes released from brown adipocytes, and in exosomes isolated from mouse serum, we show that levels of miRNAs change after BAT activation in vitro and in vivo . One of these exosomal miRNAs, miR-92a, is also present in human serum exosomes. Importantly, serum concentrations of exosomal miR-92a inversely correlate with human BAT activity measured by 18 F-FDG PET/CT in two unique and independent cohorts comprising 41 healthy individuals. Thus, exosomal miR-92a represents a potential serum biomarker for BAT activity in mice and humans. Exosomes are RNA-containing lipid vesicles with roles in inter-tissue crosstalk. Here the authors show that exosome release from brown adipocytes is increased upon thermogenic activation, both in vitro and in vivo , and demonstrate that serum levels of exosomal miR-92 reflect brown fat activity in humans.
AbstractList	Brown adipose tissue (BAT) dissipates energy and its activity correlates with leanness in human adults. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography coupled with computer tomography (PET/CT) is still the standard for measuring BAT activity, but exposes subjects to ionizing radiation. To study BAT function in large human cohorts, novel diagnostic tools are needed. Here we show that brown adipocytes release exosomes and that BAT activation increases exosome release. Profiling miRNAs in exosomes released from brown adipocytes, and in exosomes isolated from mouse serum, we show that levels of miRNAs change after BAT activation in vitro and in vivo . One of these exosomal miRNAs, miR-92a, is also present in human serum exosomes. Importantly, serum concentrations of exosomal miR-92a inversely correlate with human BAT activity measured by 18 F-FDG PET/CT in two unique and independent cohorts comprising 41 healthy individuals. Thus, exosomal miR-92a represents a potential serum biomarker for BAT activity in mice and humans. Exosomes are RNA-containing lipid vesicles with roles in inter-tissue crosstalk. Here the authors show that exosome release from brown adipocytes is increased upon thermogenic activation, both in vitro and in vivo , and demonstrate that serum levels of exosomal miR-92 reflect brown fat activity in humans. Brown adipose tissue (BAT) dissipates energy and its activity correlates with leanness in human adults. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography coupled with computer tomography (PET/CT) is still the standard for measuring BAT activity, but exposes subjects to ionizing radiation. To study BAT function in large human cohorts, novel diagnostic tools are needed. Here we show that brown adipocytes release exosomes and that BAT activation increases exosome release. Profiling miRNAs in exosomes released from brown adipocytes, and in exosomes isolated from mouse serum, we show that levels of miRNAs change after BAT activation in vitro and in vivo. One of these exosomal miRNAs, miR-92a, is also present in human serum exosomes. Importantly, serum concentrations of exosomal miR-92a inversely correlate with human BAT activity measured by (18)F-FDG PET/CT in two unique and independent cohorts comprising 41 healthy individuals. Thus, exosomal miR-92a represents a potential serum biomarker for BAT activity in mice and humans. Brown adipose tissue (BAT) dissipates energy and its activity correlates with leanness in human adults. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography coupled with computer tomography (PET/CT) is still the standard for measuring BAT activity, but exposes subjects to ionizing radiation. To study BAT function in large human cohorts, novel diagnostic tools are needed. Here we show that brown adipocytes release exosomes and that BAT activation increases exosome release. Profiling miRNAs in exosomes released from brown adipocytes, and in exosomes isolated from mouse serum, we show that levels of miRNAs change after BAT activation in vitro and in vivo . One of these exosomal miRNAs, miR-92a, is also present in human serum exosomes. Importantly, serum concentrations of exosomal miR-92a inversely correlate with human BAT activity measured by 18 F-FDG PET/CT in two unique and independent cohorts comprising 41 healthy individuals. Thus, exosomal miR-92a represents a potential serum biomarker for BAT activity in mice and humans. Exosomes are RNA-containing lipid vesicles with roles in inter-tissue crosstalk. Here the authors show that exosome release from brown adipocytes is increased upon thermogenic activation, both in vitro and in vivo, and demonstrate that serum levels of exosomal miR-92 reflect brown fat activity in humans.
ArticleNumber	11420
Author	van Marken Lichtenbelt, Wouter Virtanen, Kirsi A. Siegel, Franziska Pfeifer, Alexander Naumann, Jennifer Pan, Ruping Buyel, Joschka J. Hanssen, Mark J. W. Schlein, Christian Schell, Michael Froehlich, Holger van der Lans, Anouk Heeren, Joerg Chen, Yong
Author_xml	– sequence: 1 givenname: Yong surname: Chen fullname: Chen, Yong organization: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, Sigmund-Freud Strasse 25, 53127 Bonn, Germany – sequence: 2 givenname: Joschka J. surname: Buyel fullname: Buyel, Joschka J. organization: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, Sigmund-Freud Strasse 25, 53127 Bonn, Germany, Research Training Group 1873, University of Bonn – sequence: 3 givenname: Mark J. W. surname: Hanssen fullname: Hanssen, Mark J. W. organization: Department of Human Biology & Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center – sequence: 4 givenname: Franziska surname: Siegel fullname: Siegel, Franziska organization: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, Sigmund-Freud Strasse 25, 53127 Bonn, Germany – sequence: 5 givenname: Ruping surname: Pan fullname: Pan, Ruping organization: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, Sigmund-Freud Strasse 25, 53127 Bonn, Germany – sequence: 6 givenname: Jennifer surname: Naumann fullname: Naumann, Jennifer organization: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, Sigmund-Freud Strasse 25, 53127 Bonn, Germany – sequence: 7 givenname: Michael surname: Schell fullname: Schell, Michael organization: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, Sigmund-Freud Strasse 25, 53127 Bonn, Germany – sequence: 8 givenname: Anouk surname: van der Lans fullname: van der Lans, Anouk organization: Department of Human Biology & Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center – sequence: 9 givenname: Christian surname: Schlein fullname: Schlein, Christian organization: Department of Biochemistry and Molecular Cell Biology, University Medical Center – sequence: 10 givenname: Holger surname: Froehlich fullname: Froehlich, Holger organization: Research Training Group 1873, University of Bonn, Bonn-Aachen International Center for Information Technology (B-IT), Institute for Computer Science, University of Bonn – sequence: 11 givenname: Joerg surname: Heeren fullname: Heeren, Joerg organization: Department of Biochemistry and Molecular Cell Biology, University Medical Center – sequence: 12 givenname: Kirsi A. surname: Virtanen fullname: Virtanen, Kirsi A. organization: Turku PET Center, Turku University Hospital, Turku PET Center, University of Turku – sequence: 13 givenname: Wouter surname: van Marken Lichtenbelt fullname: van Marken Lichtenbelt, Wouter organization: Department of Human Biology & Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center – sequence: 14 givenname: Alexander surname: Pfeifer fullname: Pfeifer, Alexander email: alexander.pfeifer@uni-bonn.de organization: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, Sigmund-Freud Strasse 25, 53127 Bonn, Germany, Research Training Group 1873, University of Bonn, PharmaCenter, University of Bonn
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PublicationDate_xml	– month: 4 year: 2016 text: 20160427 day: 27
PublicationDecade	2010
PublicationPlace	London
PublicationPlace_xml	– name: London – name: England
PublicationTitle	Nature communications
PublicationTitleAbbrev	Nat Commun
PublicationTitleAlternate	Nat Commun
PublicationYear	2016
Publisher	Nature Publishing Group UK Nature Publishing Group Nature Portfolio
Publisher_xml	– name: Nature Publishing Group UK – name: Nature Publishing Group – name: Nature Portfolio
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Snippet	Brown adipose tissue (BAT) dissipates energy and its activity correlates with leanness in human adults. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission... Brown adipose tissue (BAT) dissipates energy and its activity correlates with leanness in human adults. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission... Brown adipose tissue (BAT) dissipates energy and its activity correlates with leanness in human adults. 18 F-fluorodeoxyglucose (18 F-FDG) positron emission... Exosomes are RNA-containing lipid vesicles with roles in inter-tissue crosstalk. Here the authors show that exosome release from brown adipocytes is increased...
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SubjectTerms	13 13/106 13/109 13/44 38 38/90 631/337/384/331 631/443 692/308 692/53 Adipose tissue Adipose Tissue, Brown - metabolism Adult Animals Biomarkers Body fat Cohort Studies Exosomes - metabolism Female Humanities and Social Sciences Humans Ionizing radiation Kinases Male Mice, Inbred C57BL MicroRNAs MicroRNAs - blood multidisciplinary Science Science (multidisciplinary) Young Adult
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Title	Exosomal microRNA miR-92a concentration in serum reflects human brown fat activity
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