Combined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems

Abstract Metformin is an antidiabetic drug, which inhibits mitochondrial respiratory-chain-complex I and thereby seems to affect the cellular metabolism in many ways. It is also used for the treatment of the polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. In addition,...

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Autores principales:	Sameer S. Udhane, Balazs Legeza, Nesa Marti, Damian Hertig, Gaëlle Diserens, Jean-Marc Nuoffer, Peter Vermathen, Christa E. Flück
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2e71df7527134047b6b90c88fc3b0776
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spelling	oai:doaj.org-article:2e71df7527134047b6b90c88fc3b07762021-12-02T11:52:30ZCombined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems10.1038/s41598-017-09189-y2045-2322https://doaj.org/article/2e71df7527134047b6b90c88fc3b07762017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09189-yhttps://doaj.org/toc/2045-2322Abstract Metformin is an antidiabetic drug, which inhibits mitochondrial respiratory-chain-complex I and thereby seems to affect the cellular metabolism in many ways. It is also used for the treatment of the polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. In addition, metformin possesses antineoplastic properties. Although metformin promotes insulin-sensitivity and ameliorates reproductive abnormalities in PCOS, its exact mechanisms of action remain elusive. Therefore, we studied the transcriptome and the metabolome of metformin in human adrenal H295R cells. Microarray analysis revealed changes in 693 genes after metformin treatment. Using high resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS-NMR), we determined 38 intracellular metabolites. With bioinformatic tools we created an integrated pathway analysis to understand different intracellular processes targeted by metformin. Combined metabolomics and transcriptomics data analysis showed that metformin affects a broad range of cellular processes centered on the mitochondrium. Data confirmed several known effects of metformin on glucose and androgen metabolism, which had been identified in clinical and basic studies previously. But more importantly, novel links between the energy metabolism, sex steroid biosynthesis, the cell cycle and the immune system were identified. These omics studies shed light on a complex interplay between metabolic pathways in steroidogenic systems.Sameer S. UdhaneBalazs LegezaNesa MartiDamian HertigGaëlle DiserensJean-Marc NuofferPeter VermathenChrista E. FlückNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sameer S. Udhane Balazs Legeza Nesa Marti Damian Hertig Gaëlle Diserens Jean-Marc Nuoffer Peter Vermathen Christa E. Flück Combined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems
description	Abstract Metformin is an antidiabetic drug, which inhibits mitochondrial respiratory-chain-complex I and thereby seems to affect the cellular metabolism in many ways. It is also used for the treatment of the polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. In addition, metformin possesses antineoplastic properties. Although metformin promotes insulin-sensitivity and ameliorates reproductive abnormalities in PCOS, its exact mechanisms of action remain elusive. Therefore, we studied the transcriptome and the metabolome of metformin in human adrenal H295R cells. Microarray analysis revealed changes in 693 genes after metformin treatment. Using high resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS-NMR), we determined 38 intracellular metabolites. With bioinformatic tools we created an integrated pathway analysis to understand different intracellular processes targeted by metformin. Combined metabolomics and transcriptomics data analysis showed that metformin affects a broad range of cellular processes centered on the mitochondrium. Data confirmed several known effects of metformin on glucose and androgen metabolism, which had been identified in clinical and basic studies previously. But more importantly, novel links between the energy metabolism, sex steroid biosynthesis, the cell cycle and the immune system were identified. These omics studies shed light on a complex interplay between metabolic pathways in steroidogenic systems.
format	article
author	Sameer S. Udhane Balazs Legeza Nesa Marti Damian Hertig Gaëlle Diserens Jean-Marc Nuoffer Peter Vermathen Christa E. Flück
author_facet	Sameer S. Udhane Balazs Legeza Nesa Marti Damian Hertig Gaëlle Diserens Jean-Marc Nuoffer Peter Vermathen Christa E. Flück
author_sort	Sameer S. Udhane
title	Combined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems
title_short	Combined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems
title_full	Combined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems
title_fullStr	Combined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems
title_full_unstemmed	Combined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems
title_sort	combined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2e71df7527134047b6b90c88fc3b0776
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_version_	1718395037859971072

Combined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems

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