High-mobility group protein B1: a new biomarker of metabolic syndrome in obese children

Abstract

Introduction: Obesity is associated with a chronic low-grade inflammation. High-mobility group box 1 protein (HMGB1) plays a key role in inflammation and immunostimulatory and chemotactic processes. The aim of the study was to assess the role of HMGB1 in obese children and to evaluate its diagnostic profile in identifying childhood obesity-related complications, such as the metabolic syndrome (MS). Patients and methods: Sixty obese children were enrolled and compared with 40 healthy children (control). Homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, thyroid hormones, and pro-and anti-inflammatory peptides such as C-reactive protein (CRP), adiponectin, interleukin 6 (IL6), IL18, IL23, TNFa, resistin, and HMGB1 were evaluated. Receiver operating characteristics (ROC) analysis was employed to calculate the area under the curve (AUC) for HMGB1, IL6, and adiponectin to find the best cutoff values capable of identifying MS in obese children. Results: HMGB1 levels were statistically higher in obese patients than in the control group (19.4G6.8 vs 3.7G1.2 ng/ml; P!0.0001). In obese patients, IL18, IL6, and resistin levels were significantly high, while adiponectin levels were low. At multivariate analysis, HMGB1 was found to be independently correlated with BMI, IL23, IL6, free triiodothyronine, HDL, and HOMA-IR. At ROC analysis, HMGB1 showed higher sensitivity and specificity (AUC, 0. 992; sensitivity, 94.7%; specificity, 97.5%) than IL6 and adiponectin in identifying MS in obese children. Conclusion: HMGB1 plays an important role in the inflammatory process associated with childhood obesity. This peptide may be an important diagnostic marker for obesity-related complications, such as MS.

TLR4-dependant pro-inflammatory effects of HMGB1 on human adipocyte

“…Many studies have shown the positive correlation between circulating HMGB1 levels and BMI [8][9][10] and it has been also reported that the expression of HMGB1 in adipose tissue is altered in case of obesity. 3,8,11 This difference in HMGB1 expression has been attributed to inflammation insofar as it triggers HMGB1 secretion from cells derived from the stromal fraction of adipose tissue (ASCs), whereas mature adipocytes do not contribute to this secretion.…”

Obesity and breastfeeding: The strength of association

“…25,56 In humans, several hormone molecules, including insulin and insulin-like growth factor I (IGF-I), 57 leptin, 58 adiponectin, 59 ghrelin, 60 obestatin, 61 and resistin, 62 seem to be involved in the development of obesity. Precisely, through inflammatory factors (e.g., interleukin (IL)-6 and TNF-alpha), also found in human breast-milk, 63,64 these hormonal molecules influence fat and lean body mass development in healthy term infants, 63,64 and enhance appetite signalling, 25 promoting child satiety-responsiveness and decreasing over-eating risk. 65 …”

Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications

“…Vitamin A has been shown to induce expression of neurosteroids in glial cell lines, which could also theoretically interact with MR(s) [99]. Additionally, human fat, an active endocrine tissue, secretes various cytokines and aldosterone-releasing factors, providing another possible link to elevated ICP in obese patients with IIH (in addition to the link of aldosterone-related predisposition to arterial hypertension, insulin resistance, and metabolic syndrome in the obese population) [50, 100, 101]. …”