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Plasma metabolome study reveals metabolic changes induced by pharmacological castration and testosterone supplementation in healthy young men

de Siqueira Guedes, Jéssica ; Pla, Indira LU orcid ; Sahlin, K. Barbara LU ; Monnerat, Gustavo ; Appelqvist, Roger LU ; Marko-Varga, György LU ; Giwercman, Aleksander LU ; Domont, Gilberto Barbosa ; Sanchez, Aniel LU and Nogueira, Fábio César Sousa LU , et al. (2022) In Scientific Reports 12(1).
Abstract

Testosterone is a hormone that plays a key role in carbohydrate, fat, and protein metabolism. Testosterone deficiency is associated with multiple comorbidities, e.g., metabolic syndrome and type 2 diabetes. Despite its importance in many metabolic pathways, the mechanisms by which it controls metabolism are not fully understood. The present study investigated the short-term metabolic changes of pharmacologically induced castration and, subsequently, testosterone supplementation in healthy young males. Thirty subjects were submitted to testosterone depletion (TD) followed by testosterone supplementation (TS). Plasma samples were collected three times corresponding to basal, low, and restored testosterone levels. An untargeted... (More)

Testosterone is a hormone that plays a key role in carbohydrate, fat, and protein metabolism. Testosterone deficiency is associated with multiple comorbidities, e.g., metabolic syndrome and type 2 diabetes. Despite its importance in many metabolic pathways, the mechanisms by which it controls metabolism are not fully understood. The present study investigated the short-term metabolic changes of pharmacologically induced castration and, subsequently, testosterone supplementation in healthy young males. Thirty subjects were submitted to testosterone depletion (TD) followed by testosterone supplementation (TS). Plasma samples were collected three times corresponding to basal, low, and restored testosterone levels. An untargeted metabolomics study was performed by liquid chromatography–high resolution mass spectrometry (UHPLC–HRMS) to monitor the metabolic changes induced by the altered hormone levels. Our results demonstrated that TD was associated with major metabolic changes partially restored by TS. Carnitine and amino acid metabolism were the metabolic pathways most impacted by variations in testosterone. Furthermore, our results also indicated that LH and FSH might strongly alter the plasma levels of indoles and lipids, especially glycerophospholipids and sphingolipids. Our results demonstrated major metabolic changes induced by low testosterone that may be important for understanding the mechanisms behind the association of testosterone deficiency and its comorbidities.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
12
issue
1
article number
15931
publisher
Nature Publishing Group
external identifiers
  • scopus:85138458005
  • pmid:36151245
ISSN
2045-2322
DOI
10.1038/s41598-022-19494-w
language
English
LU publication?
yes
additional info
Funding Information: Open access funding provided by Lund University. The Brazilian National Research Council (CNPq, 308341-2019-8 (G.B.D.); 315167/2020-3 (F.C.S.N)), the Carlos Chagas Filho Rio de Janeiro State Research Foundation (FAPERJ, E-26/210.173/2018 (G.B.D.); 26/202.650/2018 (F.C.S.N.)), and the Interreg V EU program, ReproUnion 2.0 20201846 generously providing funding to support the execution of this study. Funding Information: We are grateful to the Laboratório de Apoio ao Desenvolvimento Tecnológico (LADETEC) of the Institute of Chemistry from the Federal University of Rio de Janeiro for providing high-quality infrastructure for the UHPLC–HRMS analysis. Publisher Copyright: © 2022, The Author(s).
id
3b9e1202-4a2f-4e15-bb1b-06c856d908d8
date added to LUP
2022-11-02 10:53:30
date last changed
2025-04-18 21:00:40
@article{3b9e1202-4a2f-4e15-bb1b-06c856d908d8,
  abstract     = {{<p>Testosterone is a hormone that plays a key role in carbohydrate, fat, and protein metabolism. Testosterone deficiency is associated with multiple comorbidities, e.g., metabolic syndrome and type 2 diabetes. Despite its importance in many metabolic pathways, the mechanisms by which it controls metabolism are not fully understood. The present study investigated the short-term metabolic changes of pharmacologically induced castration and, subsequently, testosterone supplementation in healthy young males. Thirty subjects were submitted to testosterone depletion (TD) followed by testosterone supplementation (TS). Plasma samples were collected three times corresponding to basal, low, and restored testosterone levels. An untargeted metabolomics study was performed by liquid chromatography–high resolution mass spectrometry (UHPLC–HRMS) to monitor the metabolic changes induced by the altered hormone levels. Our results demonstrated that TD was associated with major metabolic changes partially restored by TS. Carnitine and amino acid metabolism were the metabolic pathways most impacted by variations in testosterone. Furthermore, our results also indicated that LH and FSH might strongly alter the plasma levels of indoles and lipids, especially glycerophospholipids and sphingolipids. Our results demonstrated major metabolic changes induced by low testosterone that may be important for understanding the mechanisms behind the association of testosterone deficiency and its comorbidities.</p>}},
  author       = {{de Siqueira Guedes, Jéssica and Pla, Indira and Sahlin, K. Barbara and Monnerat, Gustavo and Appelqvist, Roger and Marko-Varga, György and Giwercman, Aleksander and Domont, Gilberto Barbosa and Sanchez, Aniel and Nogueira, Fábio César Sousa and Malm, Johan}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Plasma metabolome study reveals metabolic changes induced by pharmacological castration and testosterone supplementation in healthy young men}},
  url          = {{http://dx.doi.org/10.1038/s41598-022-19494-w}},
  doi          = {{10.1038/s41598-022-19494-w}},
  volume       = {{12}},
  year         = {{2022}},
}