LysoPC-acyl C16:0 is associated with brown adipose tissue activity in men

Abstract

Introduction: 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 × 10−4 and 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 × 10−3 and 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.