Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes

• Published in: Cellular signalling Vol. 75; p. 109735
• Main Authors: Al-Mansoori, Layla, Al-Jaber, Hend, Madani, Aisha Y., Mazloum, Nayef A., Agouni, Abdelali, Ramanjaneya, Manjunath, Abou-Samra, Abdul-Badi, Elrayess, Mohamed A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.11.2020
• Subjects: Adipogenesis; GATA-3 suppression; Inflammation; Insulin resistance; Target validation; GATA-3 suppression; Insulin resistance; Target validation; Inflammation; Adipogenesis
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2020.109735

Impaired adipogenesis plays an important role in the development of obesity-associated insulin resistance and type 2 diabetes. Adipose tissue inflammation is a crucial mediator of this process. GATA-3 plays important roles in adipogenesis and inflammation. The aim of this study is to investigate the impact of GATA-3 suppression on improving adipogenesis, lowering inflammation and reversing insulin resistance. GATA-3 levels were measured in subcutaneous (SC) and omental (OM) adipose tissues obtained from insulin sensitive (IS) and insulin resistant (IR) obese individuals during weight reduction surgeries. The effect of GATA-3 suppression on adipogenesis, expression of inflammatory cytokines and insulin resistance biomarkers was performed in 3T3L-1 mouse preadipocytes via transfection with GATA-3-specific DNAzyme. GATA-3 expression was higher in OM compared to SC adipose tissues and in stromal vascular fraction-derived differentiating preadipocytes from IR obese individuals compared to their IS counterparts. Suppression of GATA-3 expression in 3T3L-1 mouse preadipocytes with GATA-3 specific inhibitor reversed 4-hydroxynonenal-induced impaired adipogenesis and triggered changes in the expression of insulin signaling-related genes. GATA-3 inhibition also modulated the expression of IL-6 and IL-10 and lowered the expression of insulin resistance biomarkers (PAI-1 and resistin) and insulin resistance phosphoproteins (p-BAD, p-PTEN and p-GSK3β). Inhibiting GATA-3 improves adipocytes differentiation, modulates the secretion of inflammatory cytokines and improves insulin sensitivity in insulin resistant cells. Suppression of GATA-3 could be a promising tool to improve adipogenesis, restore insulin sensitivity and lower obesity-associated inflammation in insulin resistant individuals. •Suppression of GATA-3 improves adipogenesis.•Suppression of GATA-3 restores insulin sensitivity.•Suppression of GATA-3 lowers inflammation.•Targeting GATA-3 is a promising therapeutic target of insulin resistance.