Clinical investigation of lipopolysaccharide in the persistence of metabolic syndrome (MS) through the activation of GRP78-IRE1α-ASK1 signaling pathway.

Abstract

Endoplasmic reticulum stress (ERS) might play a pivotal role in the persistence of metabolic syndrome (MS). Lipopolysaccharide (LPS) derived from various gram-negative bacteria could result in the ERS. Therefore, we aimed to investigate the association between LPS and ERS in MS. We enrolled 86 patients with MS and 42 healthy people aged 35-65years. Body weight, waist circumference, blood pressure were measured. LPS, LBP and inflammation factors, fasting plasma glucose (FPG), insulin, total cholesterol (TC), triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), free fatty acid (FFA) were analyzed in blood plasma of patient's cohort. Body mass index (BMI) and HOMA-IR were calculated. The mRNA and protein expression of ERS GRP78, IRE1α, ASK1 and IKKβ, JNK1 were measured in blood plasma of patient's cohort by RT-PCR and Elisa. MS was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criterion for Asian Americans. BMI, waist circumference, blood pressure, FPG, insulin, HOMA-IR, TC, triglyceride, HDL-C, LDL-C, FFA and LPS, LBP, TNF-α, CRP, IL-1, IL-6, MCP-1 were significantly higher in patients with MS than healthy people (P < 0.001). The correlation analysis suggested that LPS were associated with TNF-α, IL-1, IL-6, MCP-1, LBP, FFA, HOMA-IR potently (P < 0.05). The marker gene and protein expressions of ERS (GRP78, IRE1α, ASK1, IKKβ and JNK) were significantly overexpressed in patients with MS and were positive correlation with LPS (P < 0.05). LPS may play an important role in mediating chronic low-grade inflammation by activating the ERS GRP78-IRE1α-ASK1 signaling pathway, contributing to the persistence of MS.