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.
Highlights
Low testosterone levels are one of the main traits of hypogonadism, causing a multidimensional metabolic syndrome characterized by obesity, diabetes, hypertension and dyslipidaemia.[1]
The same was registered for plasma concentration of arachidonic acid (AA), 5(S)-hydroxyeicosatetraenoic acid (HETE), thromboxane-A2 and prostaglandin-E2; the levels of leukotriene B4 (LTB4) were re-established after testosterone administration (Figure 2)
Our investigation revealed that plasma levels of PC were lower in hypogonadal patients, whereas a significant increase of LPC was observed, this being related to higher activity or overexpression of phospholipase-A2 (PLA2) as reported by Keleşoğlu et al[6] Greater concentrations of LPC increase cardiovascular risk via its effects on lipid metabolism[6]; PC contributes to increase fatty acids (FAs) oxidation or metabolism and lowers the cholesterol absorption in the gastrointestinal tract.[7]
Summary
Low testosterone levels are one of the main traits of hypogonadism, causing a multidimensional metabolic syndrome characterized by obesity, diabetes, hypertension and dyslipidaemia.[1]. Lipidomics has emerged as a powerful tool in the field of biomedical research for the comprehensive characterization of lipid species and the investigation of the complex metabolic networks of lipids in a biological system.[2] On the basis of homeostasis model assessment index (HOMAi), hypogonadal men can be categorized into hyper-insulinaemic ( defined as insulin-resistant) patients and normo-insulinaemic ( defined as insulin-sensitive) patients. In these two sub-groups, the inflammatory mediators increase differently and interfere with insulin signalling in different ways. Methods of lipid and metabolite extraction, along with instrument setting for their analysis, are described in detail in supplementary material
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