Research Administration Team, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Department of Anatomy, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
Am J Physiol Endocrinol Metab. 2018 Oct 1;315(4):E543-E551. doi: 10.1152/ajpendo.00408.2017. Epub 2018 Mar 27.
Several studies have demonstrated that protectins, ω-3 fatty acid-derived proresolution mediators, may ameliorate inflammation. Recently, protectin DX (PDX) was also reported to attenuate inflammation and insulin resistance in several cell types. However, the effects of PDX on inflammation in adipocytes remain ambiguous. In this study, we found that PDX treatment suppressed adipogenesis and lipid accumulation during 3T3-L1 differentiation. Treatment of differentiated 3T3-L1 cells with PDX stimulated AMP-activated protein kinase (AMPK) phosphorylation in a dose-dependent manner. PDX-induced AMPK phosphorylation blocked lipopolysaccharide (LPS)-induced secretion of proinflammatory cytokines, such as tumor necrosis factor-α and monocyte chemoattractant protein-1. Treatment of 3T3-L1 cells with PDX alleviated LPS-induced NF-κB and inhibitory factor κB phosphorylation. Furthermore, PDX treatment diminished LPS-induced impairment of insulin signaling and insulin-stimulated glucose uptake, as well as fatty acid oxidation. These effects were decreased by silencing AMPK expression with small-interfering RNA. In conclusion, the current findings suggest that PDX attenuates inflammation and insulin resistance in adipocytes via an AMPK-dependent pathway, which in turn provides evidence that PDX has anti-inflammatory and antidiabetic effects in adipocytes.
多项研究表明，保护素，即 ω-3 脂肪酸衍生的促炎症消退介质，可能改善炎症。最近，保护素 DX（PDX）也被报道可减轻几种细胞类型的炎症和胰岛素抵抗。然而，PDX 对脂肪细胞炎症的影响仍存在争议。在这项研究中，我们发现 PDX 处理可抑制 3T3-L1 分化过程中的脂肪生成和脂质积累。PDX 以剂量依赖性方式刺激分化的 3T3-L1 细胞中 AMP 激活蛋白激酶（AMPK）磷酸化。PDX 诱导的 AMPK 磷酸化阻断了脂多糖（LPS）诱导的促炎细胞因子，如肿瘤坏死因子-α和单核细胞趋化蛋白-1 的分泌。PDX 处理可减轻 LPS 诱导的 NF-κB 和抑制因子 κB 磷酸化。此外，PDX 处理可减轻 LPS 诱导的胰岛素信号转导和胰岛素刺激的葡萄糖摄取以及脂肪酸氧化受损。用小干扰 RNA 沉默 AMPK 表达后，这些作用会降低。总之，这些发现表明 PDX 通过 AMPK 依赖性途径减轻脂肪细胞中的炎症和胰岛素抵抗，这反过来为 PDX 在脂肪细胞中具有抗炎和抗糖尿病作用提供了证据。
