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

Yong Chen,Anouk Van Der Lans,Joschka J Buyel,Alexander Pfeifer,Mark J W Hanssen,Joerg Heeren,Ruping Pan,Holger Froehlich,Wouter Van Marken Lichtenbelt,Christian Schlein,Franziska Siegel,Kirsi A Virtanen,Michael Schell,Jennifer Naumann

doi:10.1038/ncomms11420

Abstract

Brown adipose tissue (BAT) dissipates energy and its activity correlates with leanness in human adults. 18F-fluorodeoxyglucose (18F-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 18F-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.

Highlights

Brown adipose tissue (BAT) dissipates energy and its activity correlates with leanness in human adults. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography coupled with computer tomography (PET/CT) is still the standard for measuring BAT activity, but exposes subjects to ionizing radiation
MiRNAs are small non-coding RNAs, which regulate protein expression in a broad range of tissues18–20. miRNAs play an important role in BAT21 and several miRNAs have been identified that control brown adipocyte differentiation including miR-106b and miR-93, miR-133, miR-378 and miR155. miRNAs regulate browning of white adipocyte and the number of mature beige adipocytes[25,26]
Considering the weight of the three adipose tissues (Supplementary Fig. 1c), 87% of the total amount of exosomes is secreted from BAT under cold conditions, whereas exosomes from WATi and WATg make up only 11% and 2%, respectively (Supplementary Fig. 1d)

Summary

Introduction

Brown adipose tissue (BAT) dissipates energy and its activity correlates with leanness in human adults. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography coupled with computer tomography (PET/CT) is still the standard for measuring BAT activity, but exposes subjects to ionizing radiation. The metabolically active fat depots in the neck and supraclavicular region of human adults contain both constitutive brown and inducible beige adipocytes[13,14,15] with deeper neck depots possessing classical brown characteristics and more superficial depots expressing beige markers[16]. Thermogenesis mediated by both brown and beige/brite adipocytes is dependent on the action of the uncoupling protein 1 (UCP-1)[17], which uncouples mitochondrial ATP production and is stimulated by fatty acids that are liberated by lipolysis[1]. BAT activation itself, for example, by cold-exposure is able to change miRNA expression patterns of brown adipocytes[23]

Methods

Results

Conclusion