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.

受损的脂肪生成在肥胖相关的胰岛素抵抗和 2 型糖尿病的发展中起着重要作用。脂肪组织炎症是这一过程的关键介质。GATA-3 在脂肪生成和炎症中起重要作用。本研究的目的是研究 GATA-3 抑制对改善脂肪生成、降低炎症和逆转胰岛素抵抗的影响。在减重手术期间从胰岛素敏感 (IS) 和胰岛素抵抗 (IR) 肥胖个体获得的皮下 (SC) 和网膜 (OM) 脂肪组织中测量 GATA-3 水平。GATA-3 抑制对脂肪生成、炎性细胞因子表达和胰岛素抵抗生物标志物的影响在 3T3L-1 小鼠前脂肪细胞中进行用 GATA-3 特异性 DNAzyme 转染。与 SC 脂肪组织相比，OM 中的 GATA-3 表达更高，IR 肥胖个体的基质血管部分衍生的分化前脂肪细胞与其 IS 对应物相比，GATA-3 表达更高。用 GATA-3 特异性抑制剂抑制 3T3L-1 小鼠前脂肪细胞中 GATA-3 的表达可以逆转 4-羟基壬烯醛诱导的脂肪生成受损并引发胰岛素信号相关基因表达的变化。GATA-3 抑制还调节了 IL-6 和 IL-10 的表达，并降低了胰岛素抵抗生物标志物（PAI-1 和抵抗素）和胰岛素抵抗磷蛋白（p-BAD、p-PTEN 和 p-GSK3β）的表达。抑制 GATA-3 可改善脂肪细胞分化、调节炎性细胞因子的分泌并改善胰岛素抵抗细胞的胰岛素敏感性。