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In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity

Impaired 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 a...

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Autores principales: Al-Jaber, Hend, Mohamed, Nura A., Govindharajan, Vijay K., Taha, Samir, John, Jomon, Halim, Sharique, Alser, Maha, Al-Muraikhy, Shamma, Anwardeen, Najeha Rizwana, Agouni, Abdelali, Elhissi, Abdelbary, Al-Naemi, Hamda A., Al-Mansoori, Layla, Elrayess, Mohamed A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569927/
https://www.ncbi.nlm.nih.gov/pubmed/36232443
http://dx.doi.org/10.3390/ijms231911142
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author Al-Jaber, Hend
Mohamed, Nura A.
Govindharajan, Vijay K.
Taha, Samir
John, Jomon
Halim, Sharique
Alser, Maha
Al-Muraikhy, Shamma
Anwardeen, Najeha Rizwana
Agouni, Abdelali
Elhissi, Abdelbary
Al-Naemi, Hamda A.
Al-Mansoori, Layla
Elrayess, Mohamed A.
author_facet Al-Jaber, Hend
Mohamed, Nura A.
Govindharajan, Vijay K.
Taha, Samir
John, Jomon
Halim, Sharique
Alser, Maha
Al-Muraikhy, Shamma
Anwardeen, Najeha Rizwana
Agouni, Abdelali
Elhissi, Abdelbary
Al-Naemi, Hamda A.
Al-Mansoori, Layla
Elrayess, Mohamed A.
author_sort Al-Jaber, Hend
collection PubMed
description Impaired 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.
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spelling pubmed-95699272022-10-17 In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity Al-Jaber, Hend Mohamed, Nura A. Govindharajan, Vijay K. Taha, Samir John, Jomon Halim, Sharique Alser, Maha Al-Muraikhy, Shamma Anwardeen, Najeha Rizwana Agouni, Abdelali Elhissi, Abdelbary Al-Naemi, Hamda A. Al-Mansoori, Layla Elrayess, Mohamed A. Int J Mol Sci Article Impaired 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. MDPI 2022-09-22 /pmc/articles/PMC9569927/ /pubmed/36232443 http://dx.doi.org/10.3390/ijms231911142 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Al-Jaber, Hend
Mohamed, Nura A.
Govindharajan, Vijay K.
Taha, Samir
John, Jomon
Halim, Sharique
Alser, Maha
Al-Muraikhy, Shamma
Anwardeen, Najeha Rizwana
Agouni, Abdelali
Elhissi, Abdelbary
Al-Naemi, Hamda A.
Al-Mansoori, Layla
Elrayess, Mohamed A.
In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity
title In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity
title_full In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity
title_fullStr In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity
title_full_unstemmed In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity
title_short In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity
title_sort in vitro and in vivo validation of gata-3 suppression for induction of adipogenesis and improving insulin sensitivity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569927/
https://www.ncbi.nlm.nih.gov/pubmed/36232443
http://dx.doi.org/10.3390/ijms231911142
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