Clinical significance of high mobility group box 1/toll-like receptor 4 in obese diabetic patients

Abstract

High mobility group box 1 (HMGB1) is an alarmin that may link to obesity and type 2 diabetes mellitus (T2DM). The present study analyzed the correlation between HMGB1/ Toll-like receptor 4 (TLR4) and certain biochemical parameters in obese (OB) diabetic patients. 40 normal glucose tolerant subjects (NGT) and 40 patients with newly diagnosed T2DM were enrolled. All patients were further divided into non-obese NGT (NGT-NOB), obese NGT (NGT-OB), non-obese T2DM (T2DM-NOB) and obese T2DM (T2DM-OB) groups according to body mass index (BMI).The levels of HMGB1 in serum were quantified using ELISA, whereas the mRNA expression levels of TLR4 in peripheral blood mononuclear cells were assessed using reverse transcription-quantitative PCR. The results suggested that the levels of HMGB1 and TLR4 were higher in NGT-OB and T2DM-NOB groups compared with those in NGT-NOB group. Similarly, the levels of these two markers were higher in T2DM-OB group compared with those in NGT-OB group. Correlation analysis indicated that the levels of HMGB1 and TLR4 were positively correlated with triglyceride (TG), fasting plasma glucose (FPG) levels and BMI, whereas a negative correlation between HMGB1 and high density lipoprotein (HDL) was noted. Linear regression analysis suggested that HMGB1 was associated with FPG and TG levels, whereas TLR4 was strongly associated with TG levels and BMI. The results demonstrated that the expression levels of HMGB1 and TLR4 in patients with T2DM or obesity were increased, which were associated with glycolipid metabolism disorders. Therefore, the HMGB1/TLR4 may serve a role in inflammatory process associated with obesity and T2DM.

MicroRNA-630 alleviates inflammatory reactions in rats with diabetic kidney disease by targeting toll-like receptor 4

“…TLR4, the first confirmed member of the toll-like family in humans, can activate signaling pathways such as the nuclear factor-kappa B and mitogen-activated protein kinase family pathways after interacting with ligands in vivo , which increases the production of inflammatory markers and activates an inflammatory response[ 30 ]. Activation of the TLR4 signaling pathway is closely related to the pathogenesis of diabetic nephropathy, and the expression of TLR4 and related inflammatory factors TNF-α, IL-6, and IL-1β increases during the occurrence and development of diabetic nephropathy[ 31 , 32 ]. This work used a bioinformatics website to predict that miR-630 may combine with the 3’-UTR of TLR4 and a twofold luciferase assay to confirm that TLR4 was the direct target of miR-630.…”

Age- and Sex- Dependent Changes in Serum Levels of TAS, TOS, TLR2, TLR4, HSP60, HSP90, and HMGB1

“…A surge in their expression results in excess activation of the inflammatory process (36). TLR2 and TLR4 have been suggested as a biomarker for many diseases, such as breast cancer (37), colorectal cancer (38), multiple sclerosis (39), acute aortic dissection (40), and diabetes (41). TLR2 and TLR4 are known as the soluble form of TLRs, which may act as an inhibitor for excessive TLR activation (36).…”