Metabolic patterns in insulin-sensitive male hypogonadism

Cell Death & Disease
Giuseppina FanelliLello Zolla

Abstract

Male hypogonadism is a disorder characterised by low levels of the hormone testosterone. At beginning subjects with low levels of testosterone do not show insulin resistance (insulin-sensitive patients), which develops over time (insulin-resistance patients). To analyse the metabolic alterations mainly related to decreased testosterone, we performed metabolomics investigations on the plasma of males with hypogonadism who showed normal insulin levels. Plasma from patients with low testosterone (<8 nmol/l) and homeostatic model assessment for insulin-resistance-index (HOMAi) < 2.5, as well as matched controls, was analysed by UHPLC and mass spectrometry. Then metabolites were then subjected to multivariate statistical analysis and grouped by metabolic pathways. Glycolysis was not altered, as expected for the presence of insulin activity, but imbalances in several other pathways were found, such as the pentose phosphate pathway (PPP), glycerol shuttle, malate shuttle, Krebs cycle (TCA) and lipid metabolism. The PPP was significantly upregulated. Moreover, while the first steps of the Krebs cycle were downregulated, 2-oxoglutarate was replenished via glutaminolysis. Since glutaminolysis leads to an activation of the malate aspartat...Continue Reading

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Jun 6, 2018·Cell Death & Disease·Federica GeviLello Zolla

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Citations

Jun 6, 2018·Cell Death & Disease·Federica GeviLello Zolla
Sep 28, 2021·Journal of Animal Physiology and Animal Nutrition·Lewei GuoJun Wang

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Methods Mentioned

BETA
metabolomics

Software Mentioned

Graphpad
Metabolite Set Enrichment Analysis ( MSEA )
Graphpad Prism
MSEA
MassMatrix
MetaboAnalyst
MetPA
MAVEN
Metabolomic Pathway Analysis ( MetPA )

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