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DNA hypermethylation of Kiss1r promoter and reduction of hepatic Kiss1r in female rats with type 2 diabetes

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cris.virtual.author-orcid0000-0002-8798-991X
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cris.virtual.author-orcid0000-0001-6981-9653
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cris.virtualsource.author-orcid1815dbc7-82a3-4ce5-8dc9-bbe17826792b
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cris.virtualsource.author-orcid06d96226-5dc5-4667-a85b-254ac606fda1
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dc.abstract.enKisspeptin, produced from the brain and peripheral tissues, may constitute an important link inmetabolic regulation in response to external cues, such as diet. The kisspeptin system is welldescribed in the brain. However, its function and regulation in the peripheral tissues, especiallyin relation to metabolic disease and sex differences, remain to be elucidated. As Kiss1 and Kiss1r,encoding for kisspeptin and kisspeptin receptors, respectively, are altered by overnutrition/fasting and regulated by DNA methylation during puberty and cancer, epigenetic mechanismsin metabolic disorders are highly probable. In the present study, we experimentally inducedtype 2 diabetes mellitus (DM2) in female Wistar rats using high-fat diet/streptozocin. Weanalysed expression and DNA methylation of Kiss1 and Kiss1r in the peripheral tissues, usingquantitative-reverse-transcription PCR (qRT-PCR) and pyrosequencing. We discovered differentialexpression of Kiss1 and Kiss1r in peripheral organs in DM2 females, as compared with healthycontrols, and the profile differed from patterns reported earlier in males. DM2 in females waslinked to the increased Kiss1 mRNA in the liver and increased Kiss1r mRNA in the liver andadipose tissue. However, Kiss1r promoter was hypermethylated in the liver, suggesting genesilencing. Indeed, the increase in DNA methylation of Kiss1r promoter was accompanied bya reduction in Kiss1r protein, implying epigenetic or translational gene repression. Our resultsdeliver novel evidence for tissue-specific differences in Kiss1 and Kiss1r expression in peripheralorgans in DM2 females and suggest DNA methylation as a player in regulation of the hepatickisspeptin system in DM2.
dc.affiliationWydział Medycyny Weterynaryjnej i Nauk o Zwierzętach
dc.affiliation.instituteKatedra Zoologii
dc.affiliation.instituteKatedra Fizjologii, Biochemii i Biostruktury Zwierząt
dc.contributor.authorZiarniak, Kamil
dc.contributor.authorYang, Tony
dc.contributor.authorBoycott, Cayla
dc.contributor.authorBeetch, Megan
dc.contributor.authorSassek, Maciej
dc.contributor.authorGrzęda, Emilia
dc.contributor.authorMa, Yuexi
dc.contributor.authorŚliwowska, Joanna Helena
dc.contributor.authorStefańska, Barbara
dc.date.access2026-02-10
dc.date.accessioned2026-02-26T12:07:18Z
dc.date.available2026-02-26T12:07:18Z
dc.date.copyright2022-09-12
dc.date.issued2022
dc.description.accesstimeat_publication
dc.description.bibliographyil., bibliogr.
dc.description.financepublication_nocost
dc.description.financecost0,00
dc.description.if3,7
dc.description.number13
dc.description.points100
dc.description.versionfinal_published
dc.description.volume17
dc.identifier.doi10.1080/15592294.2022.2119120
dc.identifier.eissn1559-2308
dc.identifier.issn1559-2294
dc.identifier.urihttps://sciencerep.up.poznan.pl/handle/item/7498
dc.identifier.weblinkhttps://www.tandfonline.com/doi/permissions/10.1080/15592294.2022.2119120?
dc.languageen
dc.relation.ispartofEpigenetics
dc.relation.pages2332–2346
dc.rightsCC-BY-NC-ND
dc.sciencecloudnosend
dc.share.typeOTHER
dc.subject.enDNA methylation
dc.subject.enkisspeptin
dc.subject.endiabetes type 2
dc.subject.enliver
dc.titleDNA hypermethylation of Kiss1r promoter and reduction of hepatic Kiss1r in female rats with type 2 diabetes
dc.typeJournalArticle
dspace.entity.typePublication
oaire.citation.issue13
oaire.citation.volume17