LysoPC-acyl C16:0 is associated with brown adipose tissue activity in men.
BACKGROUND
Brown adipose tissue (BAT) recently emerged as a potential therapeutic target in the treatment of obesity and associated disorders due to its fat-burning capacity. The current gold standard in assessing BAT activity is [18F]FDG PET-CT scan, which has severe limitations including radiation exposure, being expensive, and being labor-intensive. Therefore, indirect markers are needed of human BAT activity and volume.


OBJECTIVE
We aimed to identify metabolites in serum that are associated with BAT volume and activity in men.


METHODS
We assessed 163 metabolites in fasted serum of a cohort of twenty-two healthy lean men (age 24.1 (21.7-26.6) years, BMI 22.1 (20.5-23.4) kg/m2) who subsequently underwent a cold-induced [18F]FDG PET-CT scan to assess BAT volume and activity. In addition, we included three replication cohorts consisting of in total thirty-seven healthy lean men that were similar with respect to age and BMI compared to the discovery cohort.


RESULTS
After correction for multiple testing, fasting concentrations of lysophosphatidylcholine-acyl (LysoPC-acyl) C16:1, LysoPC-acyl C16:0 and phosphatidylcholine-diacyl C32:1 showed strong positive correlations with BAT volume (β= 116 (85-148) mL, R2= 0.81, p = 4.6 × 10-7;β = 79 (93-119) mL, R2= 0.57, p = 5.9 × 10-4and β= 91 (40-141) mL, R2= 0.52, p = 1.0 × 10-3, respectively) as well as with BAT activity (β= 0.20 (0.11-0.29) g/mL, R2= 0.59, p = 1.9 × 10-4; β = 0.15 (0.06-0.23) g/mL, R2= 0.47, p = 2.0 × 10-3and β= 0.13 (0.01-0.25) g/mL, R2= 0.28, p = 0.04, respectively). When tested in three independent replication cohorts (total n = 37), the association remained significant between LysoPC-acyl C16:0 and BAT activity in a pooled analysis (β= 0.15 (0.07-0.23) g/mL, R2= 0.08, p = 4.2 × 10-4).


CONCLUSIONS
LysoPC-acyl C16:0 is associated with BAT activity in men. Since BAT is regarded as a promising tool in the battle against obesity and related disorders, the identification of such a noninvasive marker is highly relevant.
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.|Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Mariëtte R
MR
Boon
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Leontine E H
LEH
Bakker
Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.
Cornelia
C
Prehn
Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.|German Center for Diabetes Research, Neuherberg, Germany.|Lehrstul für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany.
Jerzy
J
Adamski
Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Maarten J
MJ
Vosselman
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Ingrid M
IM
Jazet
Department of Radiology, Division of Nuclear Medicine, Leiden University Medical Center, Leiden, The Netherlands.|Department of Nuclear Medicine, Alrijne ziekenhuis, Leiderdorp, The Netherlands.
Lenka M Pereira
LMP
Arias-Bouda
Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Wouter D Marken
WDM
van Lichtenbelt
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.|Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Ko Willems
KW
van Dijk
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Patrick C N
PCN
Rensen
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.|Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Dennis O
DO
Mook-Kanamori
Brown adipose tissue; LysoPC-acyl C16:0; Metabolomics; [18F]FDG PET-CT scan