Control of Innate Immunity, Technology Research Association, Kagawa, Japan;
Control of Innate Immunity, Technology Research Association, Kagawa, Japan.
Anticancer Res. 2022 Aug;42(8):3983-3991. doi: 10.21873/anticanres.15894.
BACKGROUND/AIM: Lipopolysaccharide (LPS) is thought to be a causative agent of type 2 diabetes, because it has been shown that a single LPS stimulation in vitro induces chronic inflammation and reduces insulin signaling in adipocytes. However, oral LPS administration prevents type 2 diabetes, and this effect does not correspond to a single LPS adipocyte stimulation. In this study, the response of adipocytes to single and repeated stimulation with LPS was examined.
3T3-L1 cells were differentiated into adipocytes and stimulated with LPS once or thrice every 24 h. The expression levels of inflammatory and anti-inflammatory factors and insulin sensitivity-related factors were measured.
Single stimulation with LPS increased the mRNA and protein expression of inflammatory factors (interleukin-6 and monocyte chemotactic protein 1), but this increase was inhibited by repeated stimulation. In contrast, the mRNA expression levels of anti-inflammatory factors (proliferator-activated receptor γ and peroxisome proliferator-activated receptor gamma coactivator1 α) were increased by repeated LPS stimulation. Additionally, the mRNA expression levels of insulin sensitivity-related factors (glucose transporter type 4, insulin receptor, insulin receptor substrate 1 and thymoma viral proto-oncogene 2) in adipocytes were increased upon repeated LPS stimulation.
Repetitive LPS stimulation, unlike single stimulation of adipocytes, upregulates anti-inflammatory and insulin signaling-related factors.
背景/目的：脂多糖（LPS）被认为是 2 型糖尿病的致病因素，因为已经表明，体外单次 LPS 刺激会导致慢性炎症，并降低脂肪细胞中的胰岛素信号。然而，口服 LPS 给药可预防 2 型糖尿病，而这种作用与脂肪细胞单次 LPS 刺激不对应。在这项研究中，研究了脂肪细胞对 LPS 的单次和重复刺激的反应。
3T3-L1 细胞分化为脂肪细胞，并每 24 小时接受 LPS 一次或三次刺激。测量炎症和抗炎因子以及胰岛素敏感性相关因子的表达水平。
单次 LPS 刺激增加了炎症因子（白细胞介素 6 和单核细胞趋化蛋白 1）的 mRNA 和蛋白表达，但这种增加被重复刺激所抑制。相比之下，重复 LPS 刺激增加了抗炎因子（过氧化物酶体增殖物激活受体 γ 和过氧化物酶体增殖物激活受体 γ 共激活因子 1α）的 mRNA 表达水平。此外，在脂肪细胞中，胰岛素敏感性相关因子（葡萄糖转运蛋白 4、胰岛素受体、胰岛素受体底物 1 和胸腺瘤病毒原癌基因 2）的 mRNA 表达水平在重复 LPS 刺激下增加。
与脂肪细胞的单次刺激不同，重复 LPS 刺激会上调抗炎和胰岛素信号相关因子。
