Circulating THBS1: A Risk Factor for Nonalcoholic Fatty Liver Disease in Obese Children

Area of Science:

• Metabolic Research
• Pediatric Endocrinology
• Hepatology

Background:

• Thrombospondin 1 (THBS1) is an adipokine elevated in obese adults.
• The role of THBS1 in pediatric obesity and nonalcoholic fatty liver disease (NAFLD) requires investigation.
• Understanding THBS1's clinical significance may reveal new therapeutic targets.

Purpose of the Study:

• To assess the clinical significance of THBS1 in obese children with and without NAFLD.
• To determine the impact of metformin on THBS1 expression in a mouse model of obesity.
• To explore THBS1 as a potential biomarker for NAFLD in pediatric populations.

Main Methods:

• Cross-sectional study of 78 obese and 35 nonobese children, measuring anthropometrics, clinical data, and serum THBS1.
• THBS1 expression analysis in serum and liver tissue of diet-induced obese (DIO) mice.
• Metformin treatment administered to DIO mice to evaluate its effect on hepatic steatosis and THBS1 levels.

Main Results:

• Obese children with NAFLD exhibited higher THBS1 levels and increased SDS-BMI.
• Higher THBS1 quartiles correlated with a greater prevalence of hypo-high-density lipoprotein cholesterol (HDL-C).
• THBS1 proved a more sensitive predictor of NAFLD than leptin; metformin ameliorated hepatic steatosis and reduced hepatic THBS1 in DIO mice.

Conclusions:

• Circulating THBS1 may serve as a risk factor for NAFLD in obese children.
• Metformin demonstrates potential as a novel therapeutic agent for preventing and treating NAFLD.
• Metformin effectively decreases hepatic THBS1 expression in DIO mice, reinforcing its therapeutic relevance.