Anabolic androgenic steroids exert a selective remodeling of the plasma lipidome that mirrors the decrease of the de novo lipogenesis in the liver

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Abstract

Introduction

The abuse of anabolic androgenic steroids (AASs) is a source of public concern because of their adverse effects. Supratherapeutic doses of AASs are known to be hepatotoxic and regulate the lipoproteins in plasma by modifying the metabolism of lipids in the liver, which is associated with metabolic diseases. However, the effect of AASs on the profile of lipids in plasma is unknown.

Objectives

To describe the changes in the plasma lipidome exerted by AASs and to discuss these changes in the light of previous research about AASs and de novo lipogenesis in the liver.

Methods

We treated male Wistar rats with supratherapeutic doses of nandrolone decanoate and testosterone undecanoate. Subsequently, we isolated the blood plasma and performed lipidomics analysis by liquid chromatography-high resolution mass spectrometry.

Results

Lipid profiling revealed a decrease of sphingolipids and glycerolipids with palmitic, palmitoleic, stearic, and oleic acids. In addition, lipid profiling revealed an increase in free fatty acids and glycerophospholipids with odd-numbered chain fatty acids and/or arachidonic acid.

Conclusion

The lipid profile presented herein reports the imprint of AASs on the plasma lipidome, which mirrors the downregulation of de novo lipogenesis in the liver. In a broader perspective, this profile will help to understand the influence of androgens on the lipid metabolism in future studies of diseases with dysregulated lipogenesis (e.g. type 2 diabetes, fatty liver disease, and hepatocellular carcinoma).

Electronic supplementary material

The online version of this article (10.1007/s11306-019-1632-0) contains supplementary material, which is available to authorized users.

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Most cited references 54

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The ASA's Statement onp-Values: Context, Process, and Purpose

Ronald Wasserstein, Nicole A. Lazar (2016)

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Liver X receptors in lipid signalling and membrane homeostasis

Peter Tontonoz, Bo Wang (2018)

Liver X receptors α and β (LXRα and LXRβ) are nuclear receptors with pivotal roles in the transcriptional control of lipid metabolism. Transcriptional activity of LXRs is induced in response to elevated cellular levels of cholesterol. LXRs bind to and regulate the expression of genes that encode proteins involved in cholesterol absorption, transport, efflux, excretion and conversion to bile acids. The coordinated, tissue-specific actions of the LXR pathway maintain systemic cholesterol homeostasis and regulate immune and inflammatory responses. LXRs also regulate fatty acid metabolism by controlling the lipogenic transcription factor sterol regulatory element-binding protein 1c and regulate genes that encode proteins involved in fatty acid elongation and desaturation. LXRs exert important effects on the metabolism of phospholipids, which, along with cholesterol, are major constituents of cellular membranes. LXR activation preferentially drives the incorporation of polyunsaturated fatty acids into phospholipids by inducing transcription of the remodelling enzyme lysophosphatidylcholine acyltransferase 3. The ability of the LXR pathway to couple cellular sterol levels with the saturation of fatty acids in membrane phospholipids has implications for several physiological processes, including lipoprotein production, dietary lipid absorption and intestinal stem cell proliferation. Understanding how LXRs regulate membrane composition and function might provide new therapeutic insight into diseases associated with dysregulated lipid metabolism, including atherosclerosis, diabetes mellitus and cancer.

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Biological actions of androgens.

A D Mooradian, J E Morley, S Korenman (1987)

Though unnecessary for life itself, androgens are essential for the propagation of the species and for establishment and maintenance of the quality of life of males through their support of sexual behavior and function, muscle strength, and sense of well-being. In carrying out its many functions, T acts both as hormone and prohormone. It is an outstanding example of the diverse evolutionary utilization of a primitive informational molecule both among and within species. Not only does T act through the androgen receptor both unchanged and via 5 alpha-reduction, but it acts in tissues with a high aromatase level as an estrogen via the estrogen receptor. Furthermore, DHT, binding to the estrogen receptor, can act as an inhibitor of estrogen action. The products of androgen metabolism may also play active regulatory roles in hematopoiesis and in the regulation of certain hepatic enzymes. Table 3 summarizes the actions of secreted T in males indicating the probable effector hormone. While gross hypogonadism is uncommon, mild androgen insufficiency may be much more frequent, especially in older men, and in those receiving treatment for chronic medical conditions. It is quite possible that such individuals would benefit from appropriate androgen therapy were it available, but the current forms of replacement therapy are not very satisfactory. Better approaches are required. With the exception of a small number of secreted proteins, the products of transcription induced by androgens are not, as yet, known. When the androgen receptor gene is cloned it will be possible to identify androgen-regulated genes and their products. It will then be possible to design agents selectively producing specific desired androgenic effects.

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Author and article information

Contributors

David Balgoma:

ORCID: http://orcid.org/0000-0001-6463-4502

david.balgoma@ilk.uu.se

Journal

Journal ID (nlm-ta): Metabolomics

Journal ID (iso-abbrev): Metabolomics

Title: Metabolomics

Publisher: Springer US (New York )

ISSN (Print): 1573-3882

ISSN (Electronic): 1573-3890

Publication date (Electronic): 10 January 2020

Publication date PMC-release: 10 January 2020

Publication date (Print): 2020

Volume: 16

Issue: 1

Electronic Location Identifier: 12

Affiliations

[1 ]ISNI 0000 0004 1936 9457, GRID grid.8993.b, Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, , Uppsala University, ; Uppsala, Sweden

[2 ]ISNI 0000 0004 1936 9457, GRID grid.8993.b, The Beijer Laboratory, Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, , Uppsala University, ; Uppsala, Sweden

[3 ]Uppsala Biomedicinska Centrum BMC, Husargatan 3, Box 574, 751 23 Uppsala, Sweden

Author information

David Balgoma http://orcid.org/0000-0001-6463-4502

Article

Publisher ID: 1632

DOI: 10.1007/s11306-019-1632-0

PMC ID: 6954146

PubMed ID: 31925559

SO-VID: 36110532-70a4-48e3-b743-68a944730831

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 28 October 2019

Date accepted : 31 December 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100006353, Kjell och Märta Beijers Stiftelse;

Custom metadata

ScienceOpen disciplines: Molecular biology

Keywords: androgens,androgen receptor,estrogen receptors,lipidomics,liver x receptors

Data availability:

ScienceOpen disciplines: Molecular biology

Keywords: androgens, androgen receptor, estrogen receptors, lipidomics, liver x receptors

Anabolic androgenic steroids exert a selective remodeling of the plasma lipidome that mirrors the decrease of the de novo lipogenesis in the liver

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Abstract

Introduction

Objectives

Methods

Results

Conclusion

Electronic supplementary material

Related collections

Higher order chromatin architecture

Most cited references 54

The ASA's Statement onp-Values: Context, Process, and Purpose

Liver X receptors in lipid signalling and membrane homeostasis

Biological actions of androgens.

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Contributors

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