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

Abstract

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.

Screening Differential Expression Profiles of Urinary microRNAs in a Gentamycin-Induced Acute Kidney Injury Canine Model

“…GATA3 is also associated with impaired adipogenesis and insulin resistance. Inhibiting the function of GATA3 can promote the healthy distribution of adipose tissue, improve insulin sensitivity, and effectively reduce the risk of type 2 diabetes [58]. MAPK1, also known as ERK2, patriciates various cellular processes through the MAPK/ERK signaling pathway, including division, differentiation, and development [59].…”

Diabetes-Induced Vascular Dysfunction and Stemness Decline Investigated via Transcription Factor-Driven Genetic Switches

“…Utilizing drugs that speci cally target the PI3K/AKT/mTOR pathway could counteract the negative effects of GATA dysregulation. Since oxidative stress and in ammation can exacerbate the dysfunction of GATA factors and subsequent signaling pathways, antioxidants and anti-in ammatory agents could help stabilize these pathways and improve vascular function [127]. Diabetes-Induced Damage Disrupting Homeostasis in Vascular Cells: Diabetes-induced damage to GATA transcription factors can have signi cant implications for the homeostasis of vascular cells, speci cally affecting both vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs).…”