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AuthorAl-Jaber, Hend
AuthorMohamed, Nura A.
AuthorGovindharajan, Vijay K.
AuthorTaha, Samir
AuthorJohn, Jomon
AuthorHalim, Sharique
AuthorAlser, Maha
AuthorAl-Muraikhy, Shamma
AuthorAnwardeen, Najeha Rizwana
AuthorAgouni, Abdelali
AuthorElhissi, Abdelbary
AuthorAl-Naemi, Hamda A.
AuthorAl-Mansoori, Layla
AuthorElrayess, Mohamed A.
Available date2022-10-28T13:13:33Z
Publication Date2022-09-22
Publication NameInternational Journal of Molecular Sciences
Identifierhttp://dx.doi.org/10.3390/ijms231911142
CitationAl-Jaber, H.; Mohamed, N.A.; Govindharajan, V.K.; Taha, S.; John, J.; Halim, S.; Alser, M.; Al-Muraikhy, S.; Anwardeen, N.R.; Agouni, A.; Elhissi, A.; Al-Naemi, H.A.; Al-Mansoori, L.; Elrayess, M.A. In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity. Int. J. Mol. Sci. 2022, 23, 11142. https://doi.org/10.3390/ijms231911142
ISSN1661-6596
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85139905050&origin=inward
URIhttp://hdl.handle.net/10576/35542
AbstractImpaired adipogenesis is associated with the development of insulin resistance and an increased risk of type 2 diabetes (T2D). GATA Binding Protein 3 (GATA3) is implicated in impaired adipogenesis and the onset of insulin resistance. Therefore, we hypothesize that inhibition of GATA3 could promote adipogenesis, restore healthy fat distribution, and enhance insulin signaling. Primary human preadipocytes were treated with GATA3 inhibitor (DNAzyme hgd40). Cell proliferation, adipogenic capacity, gene expression, and insulin signaling were measured following well-established protocols. BALB/c mice were treated with DNAzyme hgd40 over a period of 2 weeks. Liposomes loaded with DNAzyme hgd40, pioglitazone (positive), or vehicle (negative) controls were administered subcutaneously every 2 days at the right thigh. At the end of the study, adipose tissues were collected and weighed from the site of injection, the opposite side, and the omental depot. Antioxidant enzyme (superoxide dismutase and catalase) activities were assessed in animals’ sera, and gene expression was measured using well-established protocols. In vitro GATA3 inhibition induced the adipogenesis of primary human preadipocytes and enhanced insulin signaling through the reduced expression of p70S6K. In vivo GATA3 inhibition promoted adipogenesis at the site of injection and reduced MCP-1 expression. GATA3 inhibition also reduced omental tissue size and PPARγ expression. These findings suggest that modulating GATA3 expression offers a potential therapeutic benefit by correcting impaired adipogenesis, promoting healthy fat distribution, improving insulin sensitivity, and potentially lowering the risk of T2D.
SponsorQatar University H3P grant number QPH3P-BRC-2021-451 (MAE, HN, LM).
Languageen
PublisherMDPI
Subjectadipogenesis
insulin resistance
insulin sensitivity
omental fat
subcutaneous fat
type II diabetes mellitus
TitleIn Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity
TypeArticle
Pagination1-12
Issue Number19
Volume Number23
ESSN1422-0067
dc.accessType Open Access


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