Abstract
IntroductionBrown 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.ObjectiveWe aimed to identify metabolites in serum that are associated with BAT volume and activity in men.MethodsWe 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.ResultsAfter 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).ConclusionsLysoPC-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.
Highlights
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
Brown adipocytes contain a wealth of mitochondria containing uncoupling protein 1 (UCP-1) that uncouples respiration from adenosine 5′ triphosphate (ATP) synthesis by allowing leakage of protons over the mitochondrial inner membrane, leading to heat production (Cannon and Nedergaard 2004)
Subjects underwent a medical screening including their medical history, a physical examination, blood chemistry tests, and an oral glucose tolerance test (OGTT) to exclude individuals with type 2 diabetes mellitus (T2DM) according to the American Diabetes Association (ADA) 2010 criteria
Summary
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. While the main function of WAT is the storage of fatty acids as triglycerides, BAT mainly oxidizes triglyceride-derived fatty acids to generate heat in response to various physiological stimuli including cold exposure (Cannon and Nedergaard 2004). Albeit that the precise long term contribution of BAT to human energy expenditure remains to be determined, stimulation of BAT activity or ‘recruitment’ of BAT is currently considered a potential preventive and therapeutic target in the combat against obesity and related diseases, such as dyslipidemia (Hoeke et al 2016) and type 2 diabetes mellitus (T2DM)
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