Anti-inflammatory and Insulin Signaling Phenotype Induced by Repeated Lipopolysaccharide Stimulation in 3T3-L1...

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.