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[{"key": "dc.contributor.advisor", "value": "Sulin Cheng", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Janne Ihalainen", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Kettunen, Emilia", "language": null, "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2017-07-07T09:38:40Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2017-07-07T09:38:40Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2017", "language": null, "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.other", "value": "oai:jykdok.linneanet.fi:1704815", "language": null, "element": "identifier", "qualifier": "other", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/54891", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Lihavuus yhdistet\u00e4\u00e4n metabolisiin sairauksiin kuten tyypin 2 diabetekseen, sek\u00e4 useiden molekyylien ja hormonien muuttuneisiin pitoisuuksiin verenkierrossa. Lihavilla henkil\u00f6ill\u00e4 muun muassa haaraketjuisten aminohappojen (BCAA) m\u00e4\u00e4r\u00e4 verenkierrossa on kohonnut. Rasvakudos osallistuu BCAA:n metaboliaan ja systeemisten tasojen s\u00e4\u00e4telyyn, ja muutokset rasvakudoksen toiminnassa ovat yhteydess\u00e4 havaittuihin, lihavuuteen liitettyihin komplikaatioihin. Ravintoaineiden jatkuva liikasaanti lis\u00e4\u00e4 rasvasolujen kehittymist\u00e4. Rasvasolut erilaistuvat esiasteistaan adipogeneesin aikana, jolloin solujen BCAA:n k\u00e4ytt\u00f6 lis\u00e4\u00e4ntyy. Estrogeenin on toisaalta havaittu est\u00e4v\u00e4n adipogeneesia, rasvakudoksen kasvua ja v\u00e4hent\u00e4v\u00e4n metabolisten sairauksien todenn\u00e4k\u00f6isyytt\u00e4. Aikaisemmin BCAA-metaboliaa ja estrogeenin vaikutuksia on tutkittu p\u00e4\u00e4asiassa ihmisen rasvakudoksesta eristetyill\u00e4 rasvasoluilla sek\u00e4 in vitro ja in vivo el\u00e4inmalleilla. T\u00e4ss\u00e4 gradussa adipogeneesia ja sen aikaisia muutoksia BCAA-metaboliaan osallistuvien geenien ilmentymisess\u00e4 tutkittiin ihmisen Simpson-Golabi-Behmel Syndrome (SGBS) rasvasoluilla. Lis\u00e4ksi haluttiin selvitt\u00e4\u00e4 estrogeenin vaikutukset adipogeneesiin ja kyseisten geenien ilmentymiseen. Rasvasolujen erilaistumista seurattiin 14 p\u00e4iv\u00e4n ajan viidess\u00e4 eri aikapisteess\u00e4, 0., 4., 7., 10. ja 14. p\u00e4iv\u00e4n\u00e4. Adipogeneesia ja BCAA-metaboliaan osallistuvien geenien ilmentymist\u00e4 tutkittiin transkriptiotasolla kvantitatiivisen PCR:n avulla, ja erilaistumisen aikaista lipidien ker\u00e4\u00e4ntymist\u00e4 soluihin seurattiin Oil Red O -v\u00e4rj\u00e4yksen avulla. Estrogeenin vaikutuksia tutkittiin altistamalla solut 24 tunnin ajan kolmelle eri estradioli (E2) -pitoisuudelle sek\u00e4 kontrollik\u00e4sittelylle ilman E2:a ennen jokaista aikapistett\u00e4, lukuun ottamatta 0. p\u00e4iv\u00e4\u00e4. Tutkittujen geenien ilmentyminen muuttui adipogeneesin aikana, ja useat BCAA-metaboliaan osallistuvat geenit ilmeniv\u00e4t voimakkaasti 4. p\u00e4iv\u00e4n\u00e4. Adipogeneesin s\u00e4\u00e4telyyn osallistuvan pparg-geenin ja isoleusiinin metaboliaan osallistuvan hadhb:n ilmentymisen voimistuminen 0. ja 4. p\u00e4iv\u00e4n v\u00e4lill\u00e4 oli tilastollisesti merkitsev\u00e4\u00e4. Adipogeneesia s\u00e4\u00e4televien tekij\u00f6iden tuotanto ja BCAA-metabolia t\u00e4ten aktivoituvat rasvasolujen erilaistumisen alkuvaiheessa. E2-k\u00e4sittelyt eiv\u00e4t vaikuttaneet merkitt\u00e4v\u00e4sti lipidien ker\u00e4\u00e4ntymiseen soluihin. 1 nM E2 toisaalta laski adipogeneesin s\u00e4\u00e4telyyn osallistuvan medag:n ilmenemist\u00e4 14. p\u00e4iv\u00e4n\u00e4 merkitsev\u00e4sti, mutta E2 ei muuten vaikuttanut merkitsev\u00e4sti adipogeneesia s\u00e4\u00e4televien geenien tai estrogeenireseptoreja koodaavien geenien ilmentymiseen. BCAA-metaboliassa, 100 nM E2 voimisti bcat1:n ilmentymist\u00e4 4. p\u00e4iv\u00e4n\u00e4, kun taas 14. p\u00e4iv\u00e4n\u00e4 1 nM E2 lis\u00e4si bcat1:n ilmentymist\u00e4 ja laski hmgcr:n ilmentymist\u00e4 verrattuna 100 nM E2 -k\u00e4sittelyyn. Tulosten perusteella voidaan olettaa, ett\u00e4 E2 voi s\u00e4\u00e4dell\u00e4 BCAA-metaboliaa geenitasolla vaikuttamalla bcat1:n ilmentymiseen adipogeneesin alku- ja loppuvaiheessa, ja hmgcr:n ilmentymiseen adipogeneesin loppuvaiheessa. Rasvasolut tulivat herkemmiksi E2:lle erilaistumisen my\u00f6t\u00e4. Erilaistumisen alkuvaiheessa suuret E2 pitoisuudet ja loppuvaiheessa pienemm\u00e4t pitoisuudet voivat aiheuttaa merkitsevi\u00e4 muutoksia geenien ilmentymisess\u00e4. Pienen otoskoon ja mahdollisten menetelm\u00e4llisten virheiden takia ty\u00f6n tuloksia tulee kuitenkin tarkastella ja tulkita kriittisesti. Lis\u00e4tutkimuksia kaivataan selvitt\u00e4m\u00e4\u00e4n, voiko E2 s\u00e4\u00e4dell\u00e4 BCAA-metaboliaa estrogeenireseptorien ei-genomisen s\u00e4\u00e4telyn kautta ja proteiinitasolla. Kaiken kaikkiaan t\u00e4m\u00e4 ty\u00f6 antaa uutta tietoa BCAA-metaboliaan osallistuvien geenien ilmentymisest\u00e4 E2-altistuksessa sek\u00e4 adipogeneesiin osallistuvan medag:n ilmentymisest\u00e4 ihmisen SGBS rasvasoluissa niiden erilaistumisen aikana.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Obesity is associated with metabolic diseases such as type 2 diabetes, as well as altered plasma levels of several hormones and nutrients. For instance, levels of branched-chain amino acids (BCAA) in circulation are elevated in obese subjects. White adipose tissue (WAT) takes part in the metabolism of these amino acids and regulation of their systemic levels, and impaired metabolism of WAT is linked to these detected, obesity-associated complications. In the body, excess of nutrients leads to increased size of adipose tissue, and increased number and size of mature adipocytes. Adipocytes differentiate from their precursor cells during adipogenesis, which is associated with increased utilization of BCAAs. However, estrogen can to inhibit adipogenesis, adipose tissue growth, and probability of metabolic diseases. Previously, BCAA metabolism and effects of estrogen have been studied mainly using human primary adipocytes, and in vitro and in vivo animal models. In this thesis, adipogenesis and adipogenesis-associated changes in expression of BCAA metabolism involved genes were studied with human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. In addition, effects of estrogen on adipogenesis and expression of these genes were assessed. Adipogenesis was followed for 14 days, at 5 different time points, at days 0, 4, 7, 10 and 14. Adipogenesis was followed at transcription level by analyzing expressions of adipogenesis-associated transcription factors and BCAA metabolism involved genes with real-time PCR, and by observing the lipid accumulation using Oil Red O staining. To assess the effects of estrogen, adipocytes were exposed to three different estradiol (E2) concentrations and a mock treatment without E2, 24 h prior to every time point, excluding the day 0. We found that expression of all studied genes changed during adipogenesis, and several genes were upregulated at day 4. Expressions of adipogenic pparg and isoleucine degradation pathway involved hadhb were significantly increased between the days 0 and 4, indicating that early differentiation stages are associated with upregulation of adipogenic transcription factors and BCAA metabolic pathway. E2 treatments didn\u2019t significantly affect lipid accumulation, or expression of adipogenic transcription factors, or estrogen receptors. However, 1 nM E2 did significantly decrease adipogenesis-associated medag expression at day 14. In BCAA metabolism, 100 nM E2 upregulated bcat1 significantly at day 4; whereas at day 14, 1 nM E2 downregulated bcat1 but upregulated hmgcr, involved in leucine degradation pathway, compared to 100 nM E2. Results, here, indicate that E2 can modify BCAA metabolism at transcription level mainly by regulating bcat1 expression at early and late stages of differentiation, and hmgcr expression at late stages. Adipocytes became more sensitive to E2 during their differentiation. While a higher E2 dose is needed to evoke marked responses in gene expression levels at early stages of adipogenesis, lower E2 doses can elicit subtle but significant responses at later stages. Due to the small sample size and possible errors during the study, these findings should be interpreted with caution. To assess whether E2 can regulate BCAA metabolism through estrogen receptor mediated nongenomic effects and at protein level, more studies should be made. Overall, this study provides new information about E2 regulation of genes in BCAA metabolism and expression of adipogenesis-associated medag in human SGBS preadipocytes during their differentiation.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted using Plone Publishing form by Emilia Kettunen (laemkett) on 2017-07-07 09:38:39.536762. Form: Pro gradu -lomake (https://kirjasto.jyu.fi/julkaisut/julkaisulomakkeet/pro-gradu-lomake). 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No. of bitstreams: 2\nURN:NBN:fi:jyu-201707073266.pdf: 1670400 bytes, checksum: 8601001eb4ebfc45c28d44618650ef66 (MD5)\nlicense.html: 1152 bytes, checksum: d5bfa91b224faa49647bee5309c284b7 (MD5)\n Previous issue date: 2017", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "1 verkkoaineisto (58 sivua)", "language": null, "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "schema": "dc"}, {"key": "dc.language.iso", "value": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "Rasvasolut", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "Adipogeneesi", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "Adipogenesis", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "Gene expression", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "Cell differentiation", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "BCAA-metabolia", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "E2", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "geenin ilmentyminen", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "ihmisen SGBS rasvasolut", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "BCAA metabolism", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "human SGBS preadipocytes", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "adipogenesis", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "gene expression", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Branched-chain amino acid metabolism and estrogen modification during adipogenesis", "language": null, "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-201707073266", "language": null, "element": 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