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

Endocr J. 2022 Mar 28;69(3):235-242. doi: 10.1507/endocrj.EJ21-0381. Epub 2021 Oct 15.

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.

Keywords: High mobility group box 1; Obesity; Regression analysis; Toll-like receptor 4; Type 2 diabetes mellitus.

MeSH terms

  • Body Mass Index
  • Diabetes Mellitus, Type 2* / complications
  • HMGB1 Protein
  • Humans
  • Leukocytes, Mononuclear
  • Obesity / complications
  • Toll-Like Receptor 4* / genetics

Substances

  • HMGB1 Protein
  • HMGB1 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 4