BackgroundObesity is one of the leading causes of insulin resistance. Accumulating reports have highlighted that serum amyloid A-1 (SAA1) is a potential candidate that is capable of attenuating insulin resistance. Hence, we conducted the current study with aims of investigating our proposed hypothesis that silencing SAA1 could inhibit the progression of obesity-induced insulin resistance through the NF-κB pathway.MethodsGene expression microarray analysis was initially performed to screen differentially expressed genes (DEGs) associated with obesity. Palmitate (PA)-induced insulin resistance Huh7 cell models and high-fat diet (HFD)-induced mouse models were established to elucidate the effect of SAA1/Saa1 on insulin resistance. The NF-κB pathway-related expression was subsequently determined through the application of reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis.ResultsSaa1 was identified as an obesity-related gene based on the microarray data of GSE39549. Saa1 was determined to be highly expressed in HFD-induced insulin resistance mouse models. PA-induced Huh7 cells, treated with silenced SAA1 or NF-κB pathway inhibition using BAY 11–7082, displayed a marked decrease in both Saa1 and SOCS3 as well as an elevation in 2DG, IRS1 and the extent of IRS1 phosphorylation. HFD mice treated with silenced Saa1 or inhibited NF-κB pathway exhibited improved fasting blood glucose (FBG) levels as well as fasting plasma insulin (FPI) levels, glucose tolerance and systemic insulin sensitivity. Saa1/SAA1 was determined to show a stimulatory effect on the transport of the NF-κBp65 protein from the cytoplasm to the nucleus both in vivo and in vitro, suggesting that Saa1/SAA1 could activate the NF-κB pathway.ConclusionTaken together, our key findings highlight a novel mechanism by which silencing of SAA1 hinders PA or HFD-induced insulin resistance through inhibition of the NF-κB pathway.

中文翻译：

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沉默 SAA1 通过抑制 NF-κB 通路抑制棕榈酸酯或高脂肪饮食诱导的胰岛素抵抗

背景肥胖是胰岛素抵抗的主要原因之一。越来越多的报告强调，血清淀粉样蛋白 A-1 (SAA1) 是一种能够减轻胰岛素抵抗的潜在候选者。因此，我们进行了当前的研究，目的是调查我们提出的假设，即沉默 SAA1 可以通过 NF-κB 途径抑制肥胖诱导的胰岛素抵抗的进展。与肥胖。建立棕榈酸酯（PA）诱导的胰岛素抵抗 Huh7 细胞模型和高脂饮食（HFD）诱导的小鼠模型，以阐明 SAA1/Saa1 对胰岛素抵抗的影响。随后应用逆转录定量聚合酶链反应（RT-qPCR）和蛋白质印迹分析确定NF-κB通路相关的表达。结果基于GSE39549的微阵列数据，Saa1被鉴定为肥胖相关基因。Saa1 被确定在 HFD 诱导的胰岛素抵抗小鼠模型中高度表达。PA 诱导的 Huh7 细胞，使用 BAY 11-7082 用沉默的 SAA1 或 NF-κB 通路抑制处理，显示出 Saa1 和 SOCS3 的显着减少以及 2DG、IRS1 和 IRS1 磷酸化程度的升高。用沉默的 Saa1 或抑制的 NF-κB 通路治疗的 HFD 小鼠表现出改善的空腹血糖 (FBG) 水平以及空腹血浆胰岛素 (FPI) 水平、葡萄糖耐量和全身胰岛素敏感性。