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. 2020 Jul;24(14):8266-8269.
doi: 10.1111/jcmm.15392. Epub 2020 Jun 3.

Testosterone replacement therapy in insulin-sensitive hypogonadal men restores phosphatidylcholine levels by regulation of arachidonic acid metabolism

Giuseppina Fanelli  1 , Antonio Belardo  1 , Rocco Savino  2 , Sara Rinalducci  1 , Lello Zolla  3
Affiliations

Testosterone replacement therapy in insulin-sensitive hypogonadal men restores phosphatidylcholine levels by regulation of arachidonic acid metabolism

Giuseppina Fanelli et al. J Cell Mol Med. 2020 Jul.

Abstract

Male hypogonadism is notoriously associated with altered lipid metabolism. In this study, we performed an untargeted mass spectrometry-based profiling of plasma lipids from twenty healthy and twenty hypogonadal men before and after testosterone replacement therapy (TRT) for 60 days. Results demonstrated that hypogonadism was associated with a significant increase in sphingomyelin (SM), whereas phosphatidylcholine (PC) was mainly cleaved by activated phospholipase-A2 into lysophosphatidylcholine (LPC). In hypogonadal patients, arachidonic acid (AA), also produced through the latter cleavage, was prevalently bio-transformed into leukotriene B4 (LTB4) and not into endoperoxides from which prostaglandins and thromboxanes are derived. Interestingly, upon testosterone treatment SM, PC and LPC returned to levels similar to controls. Also, AA was newly converted into prostaglandin-A2, thromboxane-A2 and 5(S)-hydroxyeicosatetraenoic acid (HETE), suggesting that testosterone probably plays a role in controlling hypogonadal alterations above reported.

Keywords: arachidonic acid metabolism; hypogonadism; lipidomics; testosterone replacement therapy.

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Conflict of interest statement

All authors declare that there is no duality of interest associated with their contribution to this manuscript.

Figures

FIGURE 1
FIGURE 1
Analysis of plasma lipid classes. Panel A, lipid class profiles as a result of control and hypogonadal men comparison. Inset shows a zoom of lipid classes with low intensities. Panel B, lipid class profiles from hypogonadal men before and after testosterone replacement therapy (TRT). FAs, fatty acids; LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine; LPEt, lysophosphatidylethanolamine‐t; PC, phosphatidylcholine; PE, phosphatidylethanolamine; SM, sphingomyelin. Asterisks indicate statistical significance (Student's t test: *P < 0.05, **P < 0.01, ***P < 0.001)
FIGURE 2
FIGURE 2
Analysis of key metabolites from the arachidonic acid pathway. Data are expressed as mean ± SD (n = 20). Asterisks indicate statistically significant differences between groups (Student's t test: *P < 0.05). 5(S)‐HETE, 5(S)‐hydroxyeicosatetraenoic acid; LPC, lysophosphatidylcholine; PC, phosphatidylcholine; TRT, testosterone replacement therapy
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