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Metabolic dynamics of human Sertoli cells are differentially modulated by physiological and pharmacological concentrations of GLP-1

2019Journal article Open access
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dc.contributor.authorMartins, Ana D.
dc.contributor.authorMonteiro, Mariana P.
dc.contributor.authorSilva, Branca M.
dc.contributor.authorBarros, Alberto
dc.contributor.authorSousa, Mário
dc.contributor.authorCarvalho, Rui A.
dc.contributor.authorOliveira, P.F.
dc.contributor.authorAlves, Marco G.
dc.date.accessioned2020-02-14T17:21:29Z
dc.date.available2020-02-14T17:21:29Z
dc.date.issued2019
dc.description.abstractObesity incidence has pandemic proportions and is expected to increase even further. Glucagon-like peptide-1 (GLP-1) based therapies are well-established pharmacological resources for obesity treatment. GLP-1 regulates energy and glucose homeostasis, which are also crucial for spermatogenesis. Herein, we studied the GLP-1 effects in human Sertoli cells (hSCs) metabolism and mitochondrial function. hSCs were cultured in absence or exposed to increasing doses of GLP-1 mimicking physiological post-prandial (0.01 nM) levels or equivalent to pharmacological levels (1 and 100 nM) used for obesity treatment. We identified GLP-1 receptor in hSCs. Consumption/production of extracellular metabolites were assessed, as well as protein levels or activities of glycolysis-related enzymes and transporters. Mitochondrial membrane potential and oxidative damage were evaluated. Glucose consumption decreased, while lactate production increased in hSCs exposed to 0.01 and 1 nM GLP-1. Though lactate dehydrogenase (LDH) protein decreased after exposure to 100 nM GLP-1 its activity increased in hSCs exposed to the same concentration of GLP-1. Mitochondrial membrane potential decreased in hSCs exposed to 100 nM of GLP-1, while formation of carbonyl groups was decreased in those cells. Those effects were followed by an increase in p-mammalian target of rapamycin (mTOR) Ser(2448). Overall, the lowest concentrations of GLP-1 increased the efficiency of glucose conversion to lactate, while GLP-1 concentration of 100 nM induces mTOR phosphorylation, decreases mitochondrial membrane potential and oxidative damage. GLP-1 regulates testicular energy homeostasis and pharmacological use of GLP-1 analogues could be valuable to counteract the negative impact of obesity in male reproductive function.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.taap.2018.10.009pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/9277
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationObesitility – Gut hormones and testicular metabolism: mechanisms associated with obesity-related male infertility
dc.relationIs insulin-regulated nutrient transport through Sertoli cell barrier in the basis of diabetes-associated male subfertility/infertility
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCells Culturedpt_PT
dc.subjectEnergy Metabolismpt_PT
dc.subjectGlucagon-Like Peptide 1pt_PT
dc.subjectGlucagon-Like Peptide-1 Receptorpt_PT
dc.subjectGlucosept_PT
dc.subjectHumanspt_PT
dc.subjectLactic Acidpt_PT
dc.subjectMalept_PT
dc.subjectMembrane Potential Mitochondrialpt_PT
dc.subjectSertoli Cellspt_PT
dc.titleMetabolic dynamics of human Sertoli cells are differentially modulated by physiological and pharmacological concentrations of GLP-1pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleObesitility – Gut hormones and testicular metabolism: mechanisms associated with obesity-related male infertility
oaire.awardTitleIs insulin-regulated nutrient transport through Sertoli cell barrier in the basis of diabetes-associated male subfertility/infertility
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FBIM-MET%2F4712%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FMEC-AND%2F28691%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_NORTE/SFRH%2FBD%2F108726%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/PEst-OE%2FSAU%2FUI0215%2F2014/PT
oaire.citation.endPage8pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleToxicology and Applied Pharmacologypt_PT
oaire.citation.volume362pt_PT
oaire.fundingStream9471 - RIDTI
oaire.fundingStream9471 - RIDTI
oaire.fundingStreamPOR_NORTE
oaire.fundingStream5876
person.familyNameMonteiro
person.familyNameSilva
person.familyNameOliveira
person.familyNameAlves
person.givenNameMariana
person.givenNameBranca Maria
person.givenNamePedro Fontes
person.givenNameMarco G.
person.identifierR-000-958
person.identifier1033309
person.identifier2358493
person.identifier.ciencia-id4014-C7BC-ED88
person.identifier.ciencia-idBD1F-B24D-89A9
person.identifier.ciencia-id9F16-B704-C407
person.identifier.ciencia-id7915-53C7-40C2
person.identifier.orcid0000-0002-0662-1831
person.identifier.orcid0000-0002-5610-8024
person.identifier.orcid0000-0002-4989-5699
person.identifier.orcid0000-0001-7635-783X
person.identifier.ridG-4795-2010
person.identifier.scopus-author-id12243571300
person.identifier.scopus-author-id7005615589
person.identifier.scopus-author-id36198848500
person.identifier.scopus-author-id57202054274
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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