Protectin DX attenuates LPS-induced inflammation and insulin resistance in adipocytes via AMPK-mediated suppression of the NF-κB pathway.

Abstract

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.