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

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.

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

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.

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).

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.