Supplementary Material for: Circulating thrombospondin 1 (THBS1): A a risk factor for Non-Alcoholic Fatty Liver Disease in obese children.

Objective: Thrombospondin 1 (THBS1) is a highly expressed adipokine in adults with obesity. In the present study, we aimed to investigate the clinical significance of THBS1in children with obesity and non-alcoholic fatty liver disease (NAFLD), and determine the effect of metformin on THBS1 expression in dietary-induced obese (DIO) mice. Methods: A cross-sectional study was conducted among 78 obese children and 35 ono-obese children. Anthropometric parameters, clinical data and circulating THBS1 levels were measured. The expression of THBS1 was detected in the serum and liver tissue from diet-induced obese mice (C57BL/6) with or without metformin treatment. Results: Higher THBS1 levels were observed in children with NAFLD and higher SDS-BMI. Individuals in the higher THBS1 quartile had a higher prevalence of hypo-high-density lipoprotein cholesterol (HDL-C). Logistics regression analysis showed a significant correlation between THBS1 and NAFLD, as well as between hip circumference and leptin levels. Receiver operating characteristic (ROC) analysis revealed that THBS1 was a more sensitive predictors of NAFLD than leptin. Additionally, metformin ameliorated hepatic steatosis and decreased hepatic THBS1 expression in high fat diet (HFD) -fed mice. Conclusions: Circulating THBS1 level may be a risk factor for NAFLD in obese children. Our findings provided a novel approach of metformin administration for the prevention and treatment of NAFLD. This study also confirmed that metformin decreased the expression of hepatic THBS in DIO mice.