Palmitate‐induced IL6 expression ameliorated by chicoric acid through AMPK and SIRT1‐mediated pathway in the PBMCs of newly diagnosed type 2 diabetes patients and healthy subjects
Graphical abstract Effect of palmitate and chicoric acid on IL6 expression in PBMCs from newly diagnosed type 2 diabetes patients and healthy subjects. Palmitate increases inflammation through down regulation of pAMPK and SIRT1. Although, chicoric acid attenuates inflammation via increasing pAMPK and SIRT1. Figure. No Caption available. HighlightsIL6 expression was higher and SIRT1 expression and pAMPK level were lower in PBMCs of diabetic patients and obese subjects.CA ameliorates IL6 both in mRNA and protein levels in palmitate‐treated PBMCs.Decreased SIRT1 gene expression and pAMPK levels induced by palmitate have been restored via CA. ABSTRACT Inhibition of inflammation is one of the possible therapeutic approaches for Insulin resistance (IR) during type 2 diabetes mellitus (T2DM). In the current study we investigated the effects of palmitate and chicoric acid (CA) on inflammation in peripheral blood mononuclear cells (PBMCs) of newly diagnosed T2DM patients and healthy subjects and explored the mechanism by which palmitate and CA influence inflammation. 20 newly diagnosed T2DM patients and 20 healthy subjects were recruited in our study. Blood sample were collected and PBMCs were isolated. Interleukin 6 (IL6), silent information regulator type 1 (SIRT1), AMP‐activated protein kinase (AMPK) and phospho‐AMPK (pAMPK) were evaluated both in vivo and in vitro. PBMCs were treated with palmitate and CA to investigate their effects on inflammation. IL6 and SIRT1 genes expression were evaluated by real‐time PCR. The levels of IL6 in culture medium were measured by ELISA. Proteins levels of AMPK and pAMPK in PBMCs were detected by western blotting. IL6 expression was higher and SIRT1 expression and pAMPK levels were lower in PBMCs of diabetic patients and obese subjects compared to healthy subjects and non‐obese subjects, respectively. CA significantly prevented against increased IL6 levels as well as its gene expression in PBMCs induced by palmitate. Also, CA returned reduction in SIRT1 expression and pAMPK levels mediated via palmitate to near control level. These findings reveal that CA reduces inflammation in PBMCs probably through upregulation of SIRT1 and pAMPK. Therefore, CA would be suggested as a novel agent for the treatment of T2DM.