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首页> 外文期刊>Cellular Signalling >Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes
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Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes

机译:GATA-3的抑制增加脂肪发生,减少炎症并提高3T3L-1前脂肪细胞中的胰岛素敏感性

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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-GSK3 beta). 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.
机译:受损的脂肪发生在肥胖相关的胰岛素抵抗和2型糖尿病中起着重要作用。脂肪组织炎症是该过程的重要介体。 Gata-3在脂肪发生和炎症中起重要作用。本研究的目的是探讨GATA-3抑制对改善脂肪发生,降低炎症和逆转胰岛素抵抗的影响。在皮下(SC)中测量GATA-3水平,并且在减少体重减轻手术期间从胰岛素敏感(IS)和胰岛素抗性(IR)肥胖个体获得的蛋白质(OM)脂肪组织。 GATA-3抑制对脂肪发生的影响,在3T3L-1小鼠前脂肪细胞中通过用GATA-3特异性DNAzyme转染在3T3L-1小鼠前脂肪细胞中进行炎症细胞因子和胰岛素抗性生物标志物的影响。与Sc脂肪组织和基质血管分数与IR肥胖个体相比,GATA-3表达较高,与SC脂肪组织和基质血管组织与IR肥胖个体相比,与其是对应物相比,从IR肥胖个体的血管分数衍生的分化。在3T3L-1小鼠前脂肪细胞中抑制GATA-3表达与GATA-3特异性抑制剂逆转4-羟基合并诱导的脂肪发生,并引发了胰岛素信号传导相关基因表达的变化。 GATA-3抑制还调节IL-6和IL-10的表达,并降低了胰岛素抗性生物标志物(PAI-1和抵抗蛋白)和胰岛素抗性磷蛋白(P-BAD,P-PTEN和P-GSK3β)的表达。抑制GATA-3改善了脂肪细胞分化,调节炎性细胞因子的分泌,提高胰岛素抗性细胞中的胰岛素敏感性。抑制GATA-3可能是提高脂肪发生,恢复胰岛素敏感性和较低肥胖相关炎症在胰岛素抗性个体中的有前途的工具。

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