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

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 [F]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/m) who subsequently underwent a cold-induced [F]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, R = 0.81, p = 4.6 × 10 β = 79 (93-119) mL, R = 0.57, p = 5.9 × 10 and β= 91 (40-141) mL, R = 0.52, p = 1.0 × 10, respectively) as well as with BAT activity (β= 0.20 (0.11-0.29) g/mL, R = 0.59, p = 1.9 × 10; β = 0.15 (0.06-0.23) g/mL, R = 0.47, p = 2.0 × 10 and β= 0.13 (0.01-0.25) g/mL, R = 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, R = 0.08, p = 4.2 × 10).

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.